臺灣博碩士論文加值系統

腦下腺前葉泌乳素（prolactin）的分泌調控主要受到結節漏斗多巴胺神經元（tuberoinfundibular dopaminergic neurons, TIDA neurons）釋放的多巴胺所抑制，其神經元本體存在於下視丘弓狀核的背中區（dorsomedial arcuate nucleus, dm ARN），而其軸突投射至中突區（median eminence, ME）。目前已知多種因子參與TIDA神經元的調控，其中包括了鴉片類物質以及多巴胺本身；無論是鴉片類胜或是其受體（mu及kappa型）均被確定存在於弓狀核，而透過它們對TIDA神經元活性產生的抑制作用也已被證實。
內嗎啡一型及二型（endomorphin-1 and -2, EM1/EM2）是一類新發現具有四個胺基酸的內生性鴉片類物質，兩者均對鴉片類受體mu型具有極高的親和力及專一性，且具有有效的止痛能力。利用免疫組織化學染色進一步證實內嗎啡存在於下視丘弓狀核。因此使我們感興趣內嗎啡的存在是否影響TIDA神經元的活性。本論文主要利用電生理及神經化學的方法探討我關心的問題。
購入的雌性大白鼠會先經過去卵巢的處理，並在一週後補充動情素再馴養一週。利用細胞外單一神經元記錄的方法對腦薄片上弓狀核背中區的神經元進行記錄，首先利用多巴胺的給予觀察該神經元是否受到抑制，以增加我們是偵測多巴胺神經元的可靠性，之後便對該神經元處理內嗎啡或鴉片類受體的拮抗劑naloxone。十七個對多巴胺產生反應的弓狀核背中區神經元中，全數受到內嗎啡一型抑制，而此抑制作用會受到naloxone的同時給予所阻斷（n=9）；三個測試內嗎啡二型的神經元中也均受到抑制。
利用側腦室注射的方法對清醒的雌性大白鼠投予藥物，內嗎啡一型及二型在每隻大鼠1 mg的劑量下能抑制TIDA神經元活性於15至60分鐘不等，但血漿中泌乳素的濃度僅在十五分鐘時有顯著上昇的現象；內嗎啡二型在三種劑量下（0.1-5 mg）均能有效抑制TIDA神經元活性，但內嗎啡二型僅在劑量1, 5 mg下使得血漿中泌乳素含量上昇；內嗎啡一型的劑量實驗中其抑制作用並不顯著。伴隨內嗎啡一型同時給予鴉片類受體的拮抗劑naloxone（2.5 mg），能有效阻斷內嗎啡一型抑制TIDA神經元活性的效果，而此時因內嗎啡一型造成的血漿泌乳素含量上昇的現象也同時被阻斷。本實驗乃利用高效液相層析儀╱電化學偵測系統測量中突區的多巴胺代謝產物DOPAC作為TIDA神經元活性之指標，以放射免疫測定法檢測血漿中泌乳素含量。
綜而言之，無論離體電生理實驗或活體神經化學實驗的結果皆支持存在於弓狀核的內嗎啡位居抑制TIDA神經元活性的地位，而此時血漿中泌乳素含量有短效上昇的趨勢。

The secretion of prolactin is inhibited by dopamine released from the tuberoinfundibular dopaminergic (TIDA) neurons. The cell bodies of these neurons are located in dorsomedial part of the hypothalamic arcuate nucleus (dmARN) and their axons terminate in the median eminence (ME). Various factors participate in the control of TIDA neurons, including the opioids and dopamine itself. Both opioid peptides and their receptors (mu and kappa subtype) are found in the ARN, and they are known to exhibit an inhibitory effect on TIDA neuronal activity.
Endomorphin-1 and -2 (EM1/EM2) are newly discovered tetrapeptides that possess high affinity and selectivity for mu opiate receptor and exhibit potent analgesic effect. Immunohistochemical staining further demonstrates that EMs are located in the ARN. Thus, it was of interest to learn if EM1 and EM2 are involved in the opioidergic control of TIDA neurons. Both electrophysiological and neurochemical approaches were adopted in the study.
Using extracellular single-unit recording of dmARN neurons in brain slices prepared from ovariectomized, estrogen-treated (OVX+E2) Sprague-Dawley rats, dmARN neurons that were inhibited by dopamine were selected first and then tested with EMs and naloxone, an opioid receptor antagonist. Of the 17 dopamine-responsive dmARN neurons, EM1 inhibited 100% of them, and its inhibitory effect could be prevented by co-administered naloxone (n=9). EM2 was tested in three dmARN neurons and it also exhibited 100% inhibition.
Using intracerebroventricular injection in conscious OVX+E2 rats, EM1 and EM2 in 1 mg/rat dose inhibited TIDA neuronal activity(determined by DOPAC level in the ME) at 15-60 min, but the serum prolactin level was significantly increased only at 15 min. While EM2 in 0.1-5 mg/rat doses was effective in inhibiting the TIDA neurons, but the serum PRL only increased in 1and 5 mg/rat doses. EM1 did not exhibit a significant dose-dependent effect either. Co-administration of naloxone in 2.5 mg/rat dose significantly blocked the inhibitory effect of EM1 on TIDA neurons, and prevented the increase in serum PRL level.
In summary, both in vitro electrophysiological and in vivo neurochemical data support the notion that EMs may play a significant inhibitory role in regulating the TIDA neuronal activity, and at the same time, it briefly stimulated the prolactin release.

目錄
英文摘要 ii
中文摘要 iv
中英名詞對照 vi
緒論 1
內嗎啡 1
泌乳素 5
結節漏斗多巴胺神經元 11
研究動機 17
實驗材料與方法 18
離體腦薄片電生理實驗 18
活體實驗 20
實驗設計與結果 25
離體腦薄片電生理實驗 25
活體實驗 26
討論 31
圖表 34
參考文獻 58

參考文獻
Abe, H., D. Engler, M. E. Molitch, J. Bollinger-Gruber, and S. Reichlin. Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat. Endocrinology, 116: 1383-1390, 1985.
Aghajanian, G. K. and B. S. Bunney. Dopamine"autoreceptors": pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedebergs Arch. Pharm., 297: 1-7, 1977.
Ahren, K., H. Fuxe, L. Hamberger, and T. Hokfelt. Turnover changes in the tubero-infundibular dopamine neurons during the ovarian cycle of the rat. Endocrinology, 88: 1415-1424, 1971.
Akil, H., S. J. Watson, E. Young, M. E. Lewis, H. Khachaturian, and J. M. Walker. Endogenous opioids: biology and function. Annu. Rev. Neurosci., 7: 223-255, 1984.
Alper, R. H., K. T. Demarest, and K. E. Moore. Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems. J. Neural Trans., 48: 157-165, 1980.
Annunziato, L. and K. E. Moore. Prolactin in CSF selectively increases dopamine turnover in the median eminence. Life Sci., 22: 2037-2041, 1978.
Asakawa, A., A. Inui, N. Ueno, M. Fujimiya, M. A. Fujino, and M. Kasuga. Endomorphin-1, an endogenous mu-opioid receptor-selective agonist, stimulates oxygen consumption in mice. Horm. Metab. Res., 32: 51-52, 2000.
Barr, G. A. and J. E. Zadina. The ontogeny of endomorphin-1- and endomorphin-2-like immunoreactivity in rat brain and spinal cord. Annu New York Acad. Sci., 897: 145-153, 1999.
Barton, A. C., R. A. Lahti, M. F. Piercey, and K. E. Moore. Autoradiographic identification of prolactin binding sites in rat median eminence. Neuroendocrinology, 49: 649-653, 1989.
Ben-Jonathan, N. Dopamine: a prolactin-inhibiting hormone. Endocrine Rev., 6: 564-589, 1985.
Ben-Jonathan, N., L. A. Arbogast, and J. F. Hyde. Neuroendocrine regulation of prolactin release Prog. Neuro., 33: 399-447, 1989.
Ben-Jonathan, N., J. L. Mershon, D. L. Allen, and R. W. Steinmetz. Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocrine Rev., 17: 639-669, 1996.
Ben-Jonathan, N., C. Oliver, H. J. Weiner, R. S. Mical, Porter, and JC. Dopamine in hypophysial portal plasma of the rat during the estrous cycle and throughout pregnancy. Endocrinology, 100: 452-458, 1977.
Boockfor, F. R., J. P. Hoeffler, and L. S. Frawley. Estradiol induces a shift in cultured cells that release prolactin or growth hormone. Am. J. Physiol., 250: E103-E105, 1986.
Bression, D., M. Michard, M. Le Dafniet, P. Pagesy, Peillon, and F. Evidence for a specific estradiol binding site on rat pituitary membranes. Endocrinology, 119: 1048-1051, 1986.
Bridges, R. S., M. Numan, P. M. Ronsheim, P. E. Mann, and C. E. Lupini. Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats. Proc. Natl. Acad. Sci. USA., 87: 8003-8007, 1990.
Bridges, R. S. and P. M. Ronsheim. Prolactin (PRL) regulation of maternal behavior in rats: bromocriptine treatment delays and PRL promotes the rapid onset of behavior. Endocrinology, 126: 837-848, 1990.
Brodie, B. B., E. Costa, A. Dlabac, N. H. Neff, and H. H. Smookler. Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J. Pharmacol. Exp. Ther., 154: 493-498, 1966.
Butcher, R. L., N. W. Fugo, and W. E. Collins. Semicircadian rhythm in plasma levels of prolactin during early gestation in the rat. Endocrinology, 90: 1125-1127, 1972.
Callahan, P., L. Grandison, and J. Rabii. Prolactin release and tuberoinfundibular dopaminergic neuronal activity following single and double injections of morphine. Brain Res., 381: 106-112, 1986.
Caron, M. G., M. Beaulieu, V. Raymond, B. Gagne, J. Drouin, R. J. Lefkowitz, and F. Labrie. Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release. J. Biol. Chem., 253: 2244-2253, 1978.
Carr, L. A. and J. L. Voogt. Catecholamine synthesizing enzymes in the hypothalamus during the estrous cycle. Brain Res., 196: 437-445, 1980.
Carter, D. A., J. M. Pennington, and S. A. Whitehead. In-vivo and in-vitro effects of domperidone on the release of prolactin and LH in male and female rats. J. Repro. Fert., 64: 191-197, 1982.
Champion, H. C., T. J. Bivalacqua, D. E. Friedman, J. E. Zadina, A. J. Kastin, Kadowitz, and PJ. Nitric oxide release mediates vasodilator responses to endomorphin 1 but not nociceptin/OFQ in the hindquarters vascular bed of the rat. Peptides 19: 1595-1602, 1998.
Champion, H. C., T. J. Bivalacqua, J. E. Zadina, A. J. Kastin, and P. J. Kadowitz. Vasodilator responses to the endomorphin peptides, but not nociceptin/OFQ, are mediated by nitric oxide release. Annu New York Acad. Sci., 897: 165-172, 1999.
Champion, H. C., J. E. Zadina, A. J. Kastin, L. Hackler, L. J. Ge, and P. J. Kadowitz. Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output, and total peripheral resistance in the rat. Peptides 18: 1393-1397, 1997.
Champion, H. C., J. E. Zadina, A. J. Kastin, and P. J. Kadowitz. Endomorphin 1 and 2 have vasodepressor activity in the anesthetized mouse. Peptides 19: 925-929, 1998.
Cramer, O. M., C. R. Parker, Jr., and J. C. Porter. Secretion of dopamine into hypophysial portal blood by rats bearing prolactin-secreting tumors or ectopic pituitary glands. Endocrinology 105: 636-640, 1979.
Creese, I., R. Schneider, and S. H. Snyder. 3H-Spiroperidol labels dopamine receptors in pituitary and brain. Eur. J. Pharmacol., 46: 377-381, 1977.
Cronin, M. J., D. A. Keefer, C. A. Valdenegro, L. G. Dabney, MacLeod, and RM. Prolactin secretion and dopamine receptors of the MtTW15 transplantable pituitary tumour. J. Endocrinol., 94: 347-358, 1982.
Czapla, M. A., H. C. Champion, J. E. Zadina, A. J. Kastin, L. Hackler, L. J. Ge, and P. J. Kadowitz. Endomorphin 1 and 2, endogenous mu-opioid agonists, decrease systemic arterial pressure in the rat. Life Sci., 62: L175-L179, 1998.
Demarest, K. T., D. W. McKay, G. D. Riegle, and K. E. Moore. Biochemical indices of tuberoinfundibular dopaminergic neuronal activity during lactation: a lack of response to prolactin. Neuroendocrinology, 36: 130-137, 1983.
Demarest, K. T. and K. E. Moore. Accumulation of L-dopa in the median eminence: an index of tuberoinfundibular dopaminergic nerve activity. Endocrinology, 106: 463-468, 1980.
Demarest, K. T. and K. E. Moore. Sexual differences in the sensitivity of tuberoinfundibular dopamine neurons to the actions of prolactin. Neuroendocrinology, 33: 230-234, 1981.
Demarest, K. T., G. D. Riegle, and K. E. Moore. Long-term treatment with estradiol induces reversible alterations in tuberoinfundibular dopaminergic neurons: a decreased responsiveness to prolactin. Neuroendocrinology, 39: 193-200, 1984.
Demarest, K. T., G. D. Riegle, and K. E. Moore. Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid 'tonic' and a delayed 'induction' component. Neuroendocrinology, 38: 467-475, 1984.
Demarest, K. T., G. D. Riegle, and K. E. Moore. Hypoprolactinemia induced by hypophysectomy and long-term bromocriptine treatment decreases tuberoinfundibular dopaminergic neuronal activity and the responsiveness of these neurons to prolactin. Neuroendocrinology, 40: 369-376, 1985.
Desjardins, G. C., J. R. Brawer, and A. Beaudet. Distribution of mu, delta, and kappa opioid receptors in the hypothalamus of the rat. Brain Res., 536: 114-123, 1990.
Deyo, S. N., R. M. Swift, and R. J. Miller. Morphine and endorphins modulate dopamine turnover in rat median eminence. Proc. Natl. Acad. Sc.USA., 76: 3006-3009, 1979.
Dudley, C. A., T. S. Jamison, and R. L. Moss. Inhibition of lordosis behavior in the female rat by intraventricular infusion of prolactin and by chronic hyperprolactinemia. Endocrinology, 110: 677-679, 1982.
Dutt, A., M. G. Kaplitt, L. M. Kow, and D. W. Pfaff. Prolactin, central nervous system and behavior: a critical review. Neuroendocrinology, 59: 413-419, 1994.
Eikenburg, D. C., A. J. Ravitz, G. A. Gudelsky, and K. E. Moore. Effects of estrogen on prolactin and tuberoinfundibular dopaminergic neurons. J. Neural Trans., 40: 235-244, 1977.
Everitt , B. J., B. Meister, T. Hokfelt, T. Melander, L. Terenius, A. Rokaeus, E. Theodorsson-Norheim, G. Dockray, J.Edwardson, C.Cuello, R. Elde, M. Goldstein, H. Hemmings, C.Ouimet, I. Walaas, P, Greengard, W. Vale, E. Weber, J.-Y. Wu and K. —J. Chang . The hypothalamic arcuate nucleus-median eminance complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons. Brain Res., 386: 97-155, 1986.
Foreman, M. M. and J. C. Porter. Prolactin augmentation of dopamine and norepinephrine release from superfused medial basal hypothalamic fragments. Endocrinology, 108: 800-804, 1981.
Fortune, J. E. and S. E. Vincent. Prolactin modulates steroidogenesis by rat granulosa cells: I. Effects on progesterone. Biol. Reprod., 35: 84-91, 1986.
Fortune, J. E., R. N. Wissler, and S. E. Vincent. Prolactin modulates steroidogenesis by rat granulosa cells: II. Effects on estradiol. Biol. Reprod., 35: 92-99, 1986.
Franks, S. and H. S. Jacobs. Hyperprolactinaemia. Clin. Endocrinol. Metab., 12: 641-668, 1983.
Frantz, A. G. Prolactin. New England J. Med., 298: 201-207, 1978.
Freeman, M. E., B. Kanyicska, A. Lerant, and G. Nagy. Prolactin: structure, function, and regulation of secretion. Physiol. Rev., 80: 1523-1631, 2000.
Freeman, M. E. and J. D. Neill. The pattern of prolactin secretion during pseudopregnancy in the rat: a daily nocturnal surge. Endocrinology, 90: 1292-1294, 1972.
Freeman, M. E., L. E. Reichert, Jr., and J. D. Neill. Regulation of the proestrus surge of prolactin secretion by gonadotropin and estrogens in the rat. Endocrinology, 90: 232-238, 1972.
Fuxe, K., T. Hokfelt, P. Eneroth, J. A. Gustafsson, and P. Skett. Prolactin-like immunoreactivity: localization in nerve terminals of rat hypothalamus. Science, 196: 899-900, 1977.
George, S. R., T. Fan, Z. Xie, R. Tse, V. Tam, G. Varghese, and B. F. O'Dowd. Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties. J. Biol. Chem., 275: 26128-26135, 2000.
Gibbs, D. M. and J. D. Neill. Dopamine levels in hypophysial stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo. Endocrinology, 102: 1895-1900, 1978.
Goffin, V., B. Bouchard, C. J. Ormandy, E. Weimann, F. Ferrag, P. Touraine, C. Bole-Feysot, R. A. Maaskant, P. Clement-Lacroix, M. Edery, N. Binart, and P. A. Kelly. Prolactin: a hormone at the crossroads of neuroimmunoendocrinology. Annu. New York Acad. Sci., 840: 498-509, 1998.
Goldberg, I. E., G. C. Rossi, S. R. Letchworth, J. P. Mathis, J. Ryan-Moro, Leventhal, L, W. Su, D. Emmel, E. A. Bolan, and G. W. Pasternak. Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain. J. Pharmacol. Exp. Ther., 286: 1007-1013, 1998.
Goldstein, A., S. Tachibana, L. I. Lowney, M. Hunkapiller, Hood, and L. Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proc. Natl. Acad. Sci. USA., 76: 6666-6670, 1979.
Grandison, L. and A. Guidotti. Regulation of prolactin release by endogenous opiates. Nature, 270: 357-359, 1977.
Grandison, L. and A. Guidotti. gamma-Aminobutyric acid receptor function in rat anterior pituitary: evidence for control of prolactin release. Endocrinology, 105: 754-759, 1979.
Gudelsky, G. A. and J. C. Porter. Morphine- and opioid peptide-induced inhibition of the release of dopamine from tuberoinfundibular neurons. Life Sci., 25: 1697-1702, 1979.
Gudelsky, G. A. and J. C. Porter. Release of dopamine from tuberoinfundibular neurons into pituitary stalk blood after prolactin or haloperidol administration. Endocrinology, 106: 526-529, 1980.
Gudelsky, G. A., J. Simpkins, G. P. Mueller, J. Meites, and K. E. Moore. Selective actions of prolactin on catecholamine turnover in the hypothalamus and on serum LH and FSH. Neuroendocrinology, 22: 206-215, 1976.
Hackler, L., J. E. Zadina, L. J. Ge, and A. J. Kastin. Isolation of relatively large amounts of endomorphin-1 and endomorphin-2 from human brain cortex. Peptides, 18: 1635-1639, 1997.
Harlan, R. E., B. D. Shivers, and D. W. Pfaff. Midbrain microinfusions of prolactin increase the estrogen-dependent behavior, lordosis. Science, 219: 1451-1453, 1983.
Harrison, L. M., A. J. Kastin, and J. E. Zadina. Differential effects of endomorphin-1, endomorphin-2, and Tyr-W-MIF-1 on activation of G-proteins in SH-SY5Y human neuroblastoma membranes. Peptides, 19: 749-753, 1998.
Haskins, J. T., G. A. Gudelsky, R. L. Moss, and J. C. Porter. Iontophoresis of morphine into the arcuate nucleus: effects on dopamine concentrations in hypophysial portal plasma and serum prolactin concentrations. Endocrinology, 108: 767-771, 1981.
Higashida, H., N. Hoshi, R. Knijnik, J. E. Zadina, and A. J. Kastin. Endomorphins inhibit high-threshold Ca2+ channel currents in rodent NG108-15 cells overexpressing mu-opioid receptors. J. Physiol., 507: 71-75, 1998.
Horrobin, D. F. Prolactin as a regulator of fluid and electrolyte metabolism in mammals. Feder. Proc., 39: 2567-2570, 1980.
Hugghins, S. Y., H. C. Champion, G. Cheng, P. J. Kadowitz, and J. R. Jeter, Jr. Vasorelaxant responses to endomorphins, nociceptin, albuterol, and adrenomedullin in isolated rat aorta. Life Sci., 67: 471-476, 2000.
Hughes, J., T. W. Smith, H. W. Kosterlitz, L. A. Fothergill, Morgan, BA, and H. R. Morris. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature, 258: 577-580, 1975.
Huhman, K. L., E. H. Mougey, T. O. Moore, and J. L. Meyerhoff. Stressors, including social conflict, decrease plasma prolactin in male golden hamsters. Horm. Behav., 29: 581-592, 1995.
Ikegami, H., H. Jikihara, K. Koike, K. Morishige, H. Kurachi, N. Yamamoto, K. Hirota, A. Miyake, and O. Tanizawa. Intraventricular administration of thyrotrophin-releasing hormone (TRH) suppresses prolactin secretion and synthesis: a possible involvement of dopamine release by TRH from rat hypothalamus. J. Endocrinol., 133: 59-66, 1992.
Jarry, H., M. Sprenger, and W. Wuttke. Rates of release of GABA and catecholamines in the mediobasal hypothalamus of ovariectomized and ovariectomized estrogen-treated rats: correlation with blood prolactin levels. Neuroendocrinology, 44: 422-428, 1986.
Jessop, D. S., G. N. Major, T. L. Coventry, S. J. Kaye, A. J. Fulford, M. S. Harbuz, De, and F. M. Bree. Novel opioid peptides endomorphin-1 and endomorphin-2 are present in mammalian immune tissues. J. Neuroimmunol. 106: 53-59, 2000.
Jiang, Y., C. M. Klodesky, and S. L. Chang. Endomorphin-1 and endomorphin-2 induce the expression of c-FOS immunoreactivity in the rat brain. Brain Res., 873: 291-296, 2000.
Kakizawa, K., I. Shimohira, S. Sakurada, T. Fujimura, K. Murayama, and H. Ueda. Parallel stimulations of in vitro and in situ [35S]GTPgammaS binding by endomorphin 1 and DAMGO in mouse brains. Peptides, 19: 755-758, 1998.
Kaplan, S. E. and A. F. De Nicola. Protein and RNA synthesis in pituitary tumors from F344 rats given implants of estrogen. J. Natl. Cancer Int., 56: 37-42, 1976.
Karashima, T. and A. V. Schally. Inhibitory effects of somatostatin analogs on prolactin secretion in rats pretreated with estrogen or haloperidol. Exp. Biol. Med., 185: 69-75, 1987.
Kawano, H. and S. Daikoku. Functional topography of the rat hypothalamic dopamine neuron systems: retrograde tracing and immunohistochemical study. J. Comp. Neurol., 265: 242-253, 1987.
Keefer, D. A., W. E. Stumpf, and P. Petrusz. Quantitative autoradiographic assessment of 3H-estradiol uptake in immunocytochemically characterized pituitary cells. Cell Tiss. Res., 166: 25-35, 1976.
Keith, L. D., B. Tam, H. Ikeda, Z. Opsahl, and M. A. Greer. Dynamics of thyrotropin-releasing hormone-induced thyrotropin and prolactin secretion by acutely dispersed rat adenohypophyseal cells. Evidence for 'all-or-none' secretion by heterogeneous secretory units, each with a specific response threshold. Neuroendocrinology, 43: 445-452, 1986.
Khalil, Z., K. Sanderson, M. Modig, and F. Nyberg. Modulation of peripheral inflammation by locally administered endomorphin-1. Inflam. Res., 48: 550-556, 1999.
Kiino, D. R. and P. S. Dannies. Insulin and 17 beta-estradiol increase the intracellular prolactin content of GH4C1 cells. Endocrinology, 109: 1264-1269, 1981.
Kwa, H. G. and F. Verhofstad. Prolactin levels in the plasma of female rats. J. Endocrinol,. 39: 455-456, 1967.
Kwok, E. H. and N. J. Dun. Endomorphins decrease heart rate and blood pressure possibly by activating vagal afferents in anesthetized rats. Brain Res., 803: 204-207, 1998.
Law, P. Y., Y. H. Wong, and H. H. Loh. Molecular mechanisms and regulation of opioid receptor signaling. Annu. Rev. Pharmacol. Toxicol., 40: 389-430, 2000.
Leadem, C. A. and S. V. Yagenova. Effects of specific activation of mu-, delta- and kappa-opioid receptors on the secretion of luteinizing hormone and prolactin in the ovariectomized rat. Neuroendocrinology, 45: 109-117, 1987.
Li, C. H. and D. Chung. Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. Proc. Natl. Acad. Scie. USA., 73: 1145-1148, 1976.
Lieberman, M. E., R. A. Maurer, and J. Gorski. Estrogen control of prolactin synthesis in vitro. Proc. Natl. Acad. Scie. USA., 75: 5946-5949, 1978.
Lin, J. Y., C. S. Li, and J. T. Pan. Effects of various neuroactive substances on single-unit activities of hypothalamic arcuate neurons in brain slices. Brain Res. Bull., 31: 587-594, 1993.
Lin, J. Y. and J. T. Pan. Effects of endogenous opioid peptides and their analogs on the activities of hypothalamic arcuate neurons in brain slices from diestrous and ovariectomized rats. Brain Res. Bul., 36: 225-233, 1995.
Lloyd, R. V. Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study. Am. J. Pathol., 113: 198-206, 1983.
Lookingland, K. J., J. M. Farah, Jr., K. L. Lovell, and K. E. Moore. Differential regulation of tuberohypophysial dopaminergic neurons terminating in the intermediate lobe and in the neural lobe of the rat pituitary gland. Neuroendocrinology, 40: 145-151, 1985.
Lookingland, K. J. and K. E. Moore. Acute effects of morphine on neurochemical estimates of activity of incertohypothalamic dopaminergic neurons in the male rat. Brain Res., 348: 205-212, 1985.
Lookingland, K. J. and K. E. Moore. Differential effects of morphine on the rates of dopamine turnover in the neural and intermediate lobes of the rat pituitary gland. Life Sci., 37: 1225-1229, 1985.
Loose, M. D. and M. J. Kelly. Opioid inhibition of spontaneously active neurons of the rat arcuate nucleus in vitro. Brain Res. Bull., 22: 819-823, 1989.
Loretz, C. A. and H. A. Bern. Prolactin and osmoregulation in vertebrates. An update. Neuroendocrinology, 35: 292-304, 1982.
Lumpkin, M. D., W. K. Samson, and S. M. McCann. Hypothalamic and pituitary sites of action of oxytocin to alter prolactin secretion in the rat. Endocrinology, 112: 1711-1717, 1983.
Lux, V. A., G. M. Somoza, and C. Libertun. beta-(-4 Chlorophenyl) GABA (baclofen) inhibits prolactin and thyrotropin release by acting on the rat brain. Exp. Biol. Med., 183: 358-362, 1986.
MacLeod, R. M., E. H. Fontham, and J. E. Lehmeyer. Prolactin and growth hormone production as influenced by catecholamines and agents that affect brain catecholamines. Neuroendocrinology, 6: 283-294, 1970.
MacMillan, S. J. and G. Clarke. Opioid peptides have differential actions on sub-populations of arcuate neurones. Life Sci., 33: 529-532, 1983.
Mai, L. M., K. R. Shieh, and J. T. Pan. Circadian changes of serum prolactin levels and tuberoinfundibular dopaminergic neuron activities in ovariectomized rats treated with or without estrogen: the role of the suprachiasmatic nuclei. Neuroendocrinology, 60: 520-526, 1994.
Malarkey, W. B., J. C. Hall, D. K. Pearl, J. K. Kiecolt-Glaser, and R. Glaser. The influence of academic stress and season on 24-hour concentrations of growth hormone and prolactin. J. Clin. Endocrinol. Metab., 73: 1089-1092, 1991.
Martin-Schild, S., A. A. Gerall, A. J. Kastin, and J. E. Zadina. Endomorphin-2 is an endogenous opioid in primary sensory afferent fibers. Peptides, 19: 1783-1789, 1998.
Martin-Schild, S., A. A. Gerall, A. J. Kastin, and J. E. Zadina. Differential distribution of endomorphin 1- and endomorphin 2-like immunoreactivities in the CNS of the rodent. J. Comp. Neurol., 405: 450-471, 1999.
Martin-Schild, S., J. E. Zadina, A. A. Gerall, S. Vigh, and A. J. Kastin. Localization of endomorphin-2-like immunoreactivity in the rat medulla and spinal cord. Peptides, 18: 1641-1649, 1997.
Maurer, R. A. Transcriptional regulation of the prolactin gene by ergocryptine and cyclic AMP. Nature, 294: 94-97, 1981.
Maurer, R. A. Estradiol regulates the transcription of the prolactin gene. J. Biol. Chem., 257: 2133-2136, 1982.
Maurer, R. A. and J. Gorski. Effects of estradiol-17beta and pimozide on prolactin synthesis in male and female rats. Endocrinology, 101: 76-84, 1977.
McConalogue, K., E. F. Grady, J. Minnis, B. Balestra, M. Tonini, N. C. Brecha, N. W. Bunnett, and C. Sternini. Activation and internalization of the mu-opioid receptor by the newly discovered endogenous agonists, endomorphin-1 and endomorphin-2. Neuroscience, 90: 1051-1059, 1999.
McNeilly, A. S., I. C. Robinson, M. J. Houston, and P. W. Howie. Release of oxytocin and prolactin in response to suckling. Br. Med. J. Clin. Res., 286: 257-259, 1983.
Mercuri, N. B., P. Calabresi, and G. Bernardi. The electrophysiological actions of dopamine and dopaminergic drugs on neurons of the substantia nigra pars compacta and ventral tegmental area. Life Sci., 51: 711-718, 1992.
Mima, H., H. Morikawa, K. Fukuda, S. Kato, T. Shoda, and K. Mori. Ca2+ channel inhibition by endomorphins via the cloned mu-opioid receptor expressed in NG108-15 cells. Eur. J. Pharmacol., 340: R1-R2, 1997.
Mizoguchi, H., M. Narita, D. E. Oji, C. Suganuma, H. Nagase, I. Sora, G. R. Uhl, E. Y. Cheng, and L. F. Tseng. The mu-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in mu-opioid receptor knockout mice. Neuroscience, 94: 203-207, 1999.
Monory, K., M. C. Bourin, M. Spetea, C. Tomboly, G. Toth, H. W. Matthes, Kieffer, BL, J. Hanoune, and A. Borsodi. Specific activation of the mu opioid receptor (MOR) by endomorphin 1 and endomorphin 2. Eur. J. Neurosci., 12: 577-584, 2000.
Moore, K. E. Interactions between prolactin and dopaminergic neurons. Biol. Reprod., 36: 47-58, 1987.
Moore, K. E. and K. J. Lookingland. Dopaminergic Neuronal Systems in the Hypothalamus. In Floyd E.Bloom and David J.Kupfer, eds. Psychopharmacology: The Fourth Generation of Progress. New York, Raven Press, Ltd. 1995, pp245-256.
Morgan, W. W. and D. C. Herbert. Early response of the dopaminergic tuberoinfundibular neurons to anterior pituitary homografts. Neuroendocrinology, 31: 215-221, 1980.
Morishige, W. K. and I. Rothchild. Temporal aspects of the regulation of corpus luteum function by luteinizing hormone, prolactin and placental luteotrophin during the first half of pregnancy in the rat. Endocrinology, 95: 260-274, 1974.
Munemura, M., T. Agui, and D. R. Sibley. Chronic estrogen treatment promotes a functional uncoupling of the D2 dopamine receptor in rat anterior pituitary gland. Endocrinology, 124: 346-355, 1989.
Neill, J. D. Effect of "stress" on serum prolactin and luteinizing hormone levels during the estrous cycle of the rat. Endocrinology, 87: 1192-1197, 1970.
Neill, J. D. Sexual differences in the hypothalamic regulation of prolactin secretion. Endocrinology, 90: 1154-1159, 1972.
Neill, J. D., M. E. Freeman, and S. A. Tillson. Control of the proestrus surge of prolactin and luteinizing hormone secretion by estrogens in the rat. Endocrinology, 89: 1448-1453, 1971.
Nevo, I., T. Avidor-Reiss, R. Levy, M. Bayewitch, and Z. Vogel. Acute and chronic activation of the mu-opioid receptor with the endogenous ligand endomorphin differentially regulates adenylyl cyclase isozymes. Neuropharmacology, 39: 364-371, 2000.
Nishiwaki, H., N. Saitoh, H. Nishio, T. Takeuchi, and F. Hata. Inhibitory effect of endomorphin-1 and -2 on acetylcholine release from myenteric plexus of guinea pig ileum. Jap. J. Pharmacol., 78: 83-86, 1998.
Ohsawa, M., H. Mizoguchi, M. Narita, M. Chu, H. Nagase, and L. F. Tseng. Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse. J. Pharmacol. Exp. Ther., 294: 1106-1111, 2000.
Owerbach, D., W. J. Rutter, N. E. Cooke, J. A. Martial, and T. B. Shows. The prolactin gene is located on chromosome 6 in humans. Science, 212: 815-816, 1981.
Pan, J. T. Neuroendocrine Functions of Dopamine. In Stone, T. W., ed. CNS Neurotransmitters and Neuromodulators Dopamine. Boca Raton, CRC Press, Inc. 1996, pp213-231.
Pan, J. T. and R. R. Gala. Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. I. Lesion studies. Endocrinology, 117: 382-387, 1985.
Pan, J. T. and R. R. Gala. Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. II. Implantation studies. Endocrinology, 117: 388-395, 1985.
Pan, J. T., L. M. Kow, and D. W. Pfaff. Single-unit activity of hypothalamic arcuate neurons in brain tissue slices. Effects of anterior pituitary hormones, cholecystokinin-octapeptide, and neurotransmitters. Neuroendocrinology, 43: 189-196, 1986.
Pasqualini, C., F. Bojda, F. Gaudoux, B. Guibert, V. Leviel, E. Teissier, R. Rips, and B. Kerdelhue. Changes in tuberoinfundibular dopaminergic neuron activity during the rat estrous cycle in relation to the prolactin surge: alteration by a mammary carcinogen. Neuroendocrinology, 48: 320-327, 1988.
Pasqualini, C., F. Bojda, and B. Kerdelhue. Direct effect of estradiol on the number of dopamine receptors in the anterior pituitary of ovariectomized rats. Endocrinology, 119: 2484-2489, 1986.
Pasqualini, C., B. Guibert, and V. Leviel. Short-term inhibitory effect of estradiol on tyrosine hydroxylase activity in tuberoinfundibular dopaminergic neurons in vitro. J. Neurochem., 60: 1707-1713, 1993.
Peroutka, S. J. 5-Hydroxytryptamine receptor subtypes: molecular, biochemical and physiological characterization. Trends Neurosci., 11: 496-500, 1988.
Peterson, P. K., G. Gekker, S. Hu, J. Lokensgard, P. S. Portoghese, and C. C. Chao. Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor. Neuropharmacology, 38: 273-278, 1999.
Pierce, T. L., M. D. Grahek, and M. W. Wessendorf. Immunoreactivity for endomorphin-2 occurs in primary afferents in rats and monkey. Neuroreport, 9: 385-389, 1998.
Pierce, T. L. and M. W. Wessendorf. Immunocytochemical mapping of endomorphin-2-immunoreactivity in rat brain. J. Chem. Neuroanat., 18: 181-207, 2000.
Porter, J. C., M. J. Reymond, J. Arita, and J. F. Sissom. Secretion of hypothalamic dopamine into the hypophysial portal vasculature: an overview. Meth. Enzymol., 103: 607-618, 1983.
Przewlocki, R., D. Labuz, J. Mika, B. Przewlocka, C. Tomboly, and G. Toth. Pain inhibition by endomorphins. Annu. New York Acad. Sci., 897: 154-164, 1999.
Rance, N., P. M. Wise, M. K. Selmanoff, and C. A. Barraclough. Catecholamine turnover rates in discrete hypothalamic areas and associated changes in median eminence luteinizing hormone-releasing hormone and serum gonadotropins on proestrus and diestrous day 1. Endocrinology, 108: 1795-1802, 1981.
Raymond, V., M. Beaulieu, F. Labrie, and J. Boissier. Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release. Science, 200: 1173-1175, 1978.
Rivier, C., J. Rivier, and W. Vale. The effect of bombesin and related peptides on prolactin and growth hormone secretion in the rat. Endocrinology, 102: 519-522, 1978.
Roth, R. H. Dopamine autoreceptors: pharmacology, function and comparison with post-synaptic dopamine receptors. Commun. Psychopharmacol., 3: 429-445, 1979.
Sakurada, S., J. E. Zadina, A. J. Kastin, S. Katsuyama, T. Fujimura, K. Murayama, M. Yuki, H. Ueda, and T. Sakurada. Differential involvement of mu-opioid receptor subtypes in endomorphin-1- and -2-induced antinociception. Eur. J. Pharmacol., 372: 25-30, 1999.
Sanchez-Blazquez, P., I. DeAntoio, M. Rodriguez-Diaz, and J. Garzon. Antisense oligodeoxynucleotide targeting distinct exons of the cloned mu-opioid receptor distinguish between endomorphin-1 and morphine supraspinal antinociception in mice. Antisense Nucleic Acid Drug Dev., 9: 253-260, 1999.
Sassin, J. F., A. G. Frantz, E. D. Weitzman, and S. Kapen. Human prolactin: 24-hour pattern with increased release during sleep. Science, 177: 1205-1207, 1972.
Schreff, M., S. Schulz, D. Wiborny, and V. Hollt. Immunofluorescent identification of endomorphin-2-containing nerve fibers and terminals in the rat brain and spinal cord. Neuroreport, 9: 1031-1034, 1998.
Selmanoff, M. The lateral and medial median eminence: distribution of dopamine, norepinephrine, and luteinizing hormone-releasing hormone and the effect of prolactin on catecholamine turnover. Endocrinology, 108: 1716-1722, 1981.
Selmanoff, M. and P. M. Wise. Decreased dopamine turnover in the median eminence in response to suckling in the lactating rat. Brain Res., 212: 101-115, 1981.
Seltzer, A., K. Tsutsumi, K. Shigematsu, and J. M. Saavedra. Reproductive hormones modulate angiotensin II AT1 receptors in the dorsomedial arcuate nucleus of the female rat. Endocrinology, 133: 939-941, 1993.
Shaar, C. J. and J. A. Clemens. The role of catecholamines in the release of anterior pituitary prolactin in vitro. Endocrinology, 95: 1202-1212, 1974.
Shangold, M. M., M. L. Gatz, and B. Thysen. Acute effects of exercise on plasma concentrations of prolactin and testosterone in recreational women runners. Fertility & Sterility, 35: 699-702, 1981.
Shennan, D. B. Regulation of water and solute transport across mammalian plasma cell membranes by prolactin. J. Dairy Res., 61: 155-166, 1994.
Shieh, K. R. and J. T. Pan. Sexual differences in the diurnal changes of tuberoinfundibular dopaminergic neuron activity in the rat: role of cholinergic control. Biol. Reprod., 54: 987-992, 1996.
Shieh, K. R. and J. T. Pan. Nicotinic control of tuberoinfundibular dopaminergic neuron activity and prolactin secretion: diurnal rhythm and involvement of endogenous opioidergic system. Brain Res., 756: 266-272, 1997.
Shin, S. H. Estradiol generates pulses of prolactin secretion in castrated male rats. Neuroendocrinology, 29: 270-275, 1979.
Shin, S. H. and C. W. Reifel. Adenohypophysis has an inherent property for pulsatile prolactin secretion. Neuroendocrinology, 32: 139-144, 1981.
Shome, B. and A. F. Parlow. Human pituitary prolactin (hPRL): the entire linear amino acid sequence. J. Clin. Endocrinol. Metab., 45: 1112-1115, 1977.
Sobrinho, L. G. The psychogenic effects of prolactin. Acta Endocrinol. 129 Suppl 1: 38-40, 1993.
Sodersten, P., S. Hansen, and P. Eneroth. Evidence that prolactin does not affect the induction of sexual behaviour by oestradiol and progesterone in ovariectomized rats. J. Endocrinol., 99: 181-187, 1983.
Sodersten, P., S. Hansen, and P. Eneroth. Inhibition of sexual behaviour in lactating rats. J. Endocrinol., 99: 189-197, 1983.
Steele, M. K., A. Negro-Vilar, and S. M. McCann. Effect of angiotensin II on in vivo and in vitro release of anterior pituitary hormones in the female rat. Endocrinology, 109: 893-899, 1981.
Stefano, G. B., Y. Goumon, F. Casares, P. Cadet, G. L. Fricchione, C. Rialas, D. Peter, D. Sonetti, M. Guarna, I. D. Welters, and E. Bianchi. Endogenous morphine. Trends Neurosci., 23: 436-442, 2000.
Stone, L. S., C. A. Fairbanks, T. M. Laughlin, H. O. Nguyen, T. M. Bushy, M. W. Wessendorf, and G. L. Wilcox. Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2. Neuroreport, 8: 3131-3135, 1997.
Tseng, L. F., M. Narita, C. Suganuma, H. Mizoguchi, M. Ohsawa, H. Nagase, and J. P. Kampine. Differential antinociceptive effects of endomorphin-1 and endomorphin-2 in the mouse. J. Pharmacol. Exp. Ther., 292: 576-583, 2000.
Vijayan, E. and S. M. McCann. In vivo and in vitro effects of substance P and neurotensin on gonadotropin and prolactin release. Endocrinology, 105: 64-68, 1979.
Vincent, S. R., T. Hokfelt, and J. Y. Wu. GABA neuron systems in hypothalamus and the pituitary gland. Immunohistochemical demonstration using antibodies against glutamate decarboxylase. Neuroendocrinology, 34: 117-125, 1982.
Voogt, J. L. and L. A. Carr. Potentiation of suckling-induced release of prolactin by inhibition of brain catecholamine synthesis. Endocrinology, 97: 891-897, 1975.
Voogt, J. L. and J. Meites. Effects of an implant of prolactin in median eminence of pseudopregnant rats on serum and pituitary LH, FSH and prolactin. Endocrinology, 88: 286-292, 1971.
Walsh, R. J., B. I. Posner, B. M. Kopriwa, and J. R. Brawer. Prolactin binding sites in the rat brain. Science, 201: 1041-1043, 1978.
Wang, X. M., K. M. Zhang, L. O. Long, C. A. Flores, and S. S. Mokha. Endomorphin-1 and endomorphin-2 modulate responses of trigeminal neurons evoked by N-methyl-D-aspartic acid and somatosensory stimuli. J. Neurophysiol. 83: 3570-3574, 2000.
West, B. and P. S. Dannies. Effects of estradiol on prolactin production and dihydroergocryptine-induced inhibition of prolactin production in primary cultures of rat pituitary cells. Endocrinology, 106: 1108-1113, 1980.
White, F. J. and R. Y. Wang. A10 dopamine neurons: role of autoreceptors in determining firing rate and sensitivity to dopamine agonists. Life Sci., 34: 1161-1170, 1984.
Yajiri, Y. and L. Y. Huang. Actions of endomorphins on synaptic transmission of Adelta-fibers in spinal cord dorsal horn neurons. J. Biomed. Sci., 7: 226-231, 2000.
Yen, S. H., C. J. Lai, J. Y. Lin, and J. T. Pan. Inhibitory effect of dopamine on dorsomedial arcuate neurons in rat brain slices: potentiation by coadministration of cocaine. Brain Res. Bull., 42: 347-351, 1997.
Yokotani, K. and Y. Osumi. Involvement of mu-receptor in endogenous opioid peptide-mediated inhibition of acetylcholine release from the rat stomach. Jap. J. Pharmacol., 78: 93-95, 1998.
Zadina, J. E., L. Hackler, L. J. Ge, and A. J. Kastin. A potent and selective endogenous agonist for the mu-opiate receptor Nature, 386: 499-502, 1997.
Zadina, J. E., S. Martin-Schild, A. A. Gerall, A. J. Kastin, L. Hackler, L. J. Ge, and X. Zhang. Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density. Annu New York Acad. Sci., 897: 136-144, 1999.