Alpha-melanocyte-stimulating hormone (α-MSH) stimulates prolactin (PRL) release and mammotrope proliferation in mouse anterior pituitary glands. The present study investigated the regulation of melanocortin-3 receptor (MC3-R) mRNA levels in mice using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Relative MC3-R mRNA levels in the anterior lobes of female mice increased between 20 and 45 days of age, and a significant difference in MC3-R mRNA expression between sexes was seen at 45 days. Ovariectomy decreased MC3-R mRNA expression in the female anterior lobes, and estradiol-17β (E2) treatment increased MC3-R mRNA levels in ovariectomized mouse anterior lobes and cultured anterior pituitary cells. E2 treatment increased proopiomelanocortin (POMC) mRNA levels in ovariectomized mouse neurointermediate lobes and cultured neurointermediate pituitary cells. On the other hand, E2 treatment did not affect POMC mRNA expression in mouse anterior lobes or cultured anterior pituitary cells. These results suggest that α-MSH directly stimulates PRL release and mammotrope proliferation through MC3-Rs expressed in mammotropes, while estrogen stimulates MC3-R gene transcription in the anterior pituitary cells and POMC gene transcription in the intermediate lobes. In lactating mice, POMC mRNA levels in the neurointermediate lobes were elevated compared with in non-lactating mice. The present study suggests that α-MSH is involved in augmented PRL secretion by estrogen and during lactation.

1.
Cone RD, Lu D, Koppula S, Vage DI, Klungland H, Boston B, Chen W, Orth DN, Pouton C, Kesterson RA: The melanocortin receptors: Agonists, antagonists, and the hormonal control of pigmentation. Recent Prog Horm Res 1996;51:287–317.
2.
Morooka Y, Oomizu S, Takeuchi S, Takahashi S: Augmentation of prolactin release by α-melanocyte stimulating hormone is possibly mediated by melanocortin 3-receptors in the mouse anterior pituitary cells. Zool Sci 1998;15:567–572.
3.
Desarnaud F, Labbé O, Eggerickx D, Vassart G, Parmentier M: Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene. Biochem J 1994;299:367–373.
4.
Matsumura R, Takagi C, Kakeya T, Okuda K, Takeuchi S, Takahashi S: α-Melanocyte-stimulating hormone stimulates prolactin secretion through melanocortin-3 receptors expressed in mammotropes in the mouse pituitary. Neuroendocrinology 2003;78:96–104.
5.
Murai I, Ben-Jonathan N: Acute stimulation of prolactin release by estradiol: Mediation by the posterior pituitary. Endocrinology 1990;126:3179–3184.
6.
Ellerkmann E, Nagy GM, Frawley LS: α-Melanocyte-stimulating hormone is a mammotrophic factor released by neurointermediate lobe cells after estrogen treatment. Endocrinology 1992;130:133–138.
7.
Hill JB, Lacy ER, Nagy GM, Gorcs TJ, Frawley LS: Does α-melanocyte-stimulating hormone from the pars intermedia regulate suckling-induced prolactin release? Supportive evidence from morphological and functional studies. Endocrinology 1993;133:2991–2997.
8.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
9.
Lamonerie T, Tremblay JJ, Lanctot C, Therrien M, Gauthier Y, Drouin J: Ptx1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene. Genes Dev 1996;10:1284–1295.
10.
Oomizu S, Takahashi S: Insulin stimulates the proliferation of mouse anterior pituitary cells in vitro. Biomed Res 1996;17:365–371.
11.
Kikuta T, Yamamoto K, Namiki H, Hayashi S: Immunocytochemical localization of estrogen receptor in various anterior pituitary hormone cells of adult male and female rats. Acta Histochem Cytochem 1993;26:609–613.
12.
Takahashi S: Development and heterogeneity of prolactin cells. Int Rev Cytol 1995;157:33–98.
13.
Hashi A, Mazawa S, Chen SY, Yamakawa K, Kato J, Arita J: Estradiol-induced diurnal changes in lactotroph proliferation and their hypothalamic regulation in ovariectomized rats. Endocrinology 1996;137:3246–3252.
14.
Oomizu S, Honda J, Takeuchi S, Kakeya T, Masui T, Takahashi S: Transforming growth factor-α stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary. J Endocrinol 2000;165:493–501.
15.
Ray D, Melmed S: Pituitary cytokine and growth factor expression and action. Endocr Rev 1997;18:206–228.
16.
Schwartz J: Intercellular communication in the anterior pituitary. Endocr Rev 2000;21:488–513.
17.
Takahashi S: Intrapituitary regulatory system of proliferation of mammotrophs in the pituitary gland. Zool Sci 2004;21:601–611.
18.
Bach MA, Bondy CA: Anatomy of the pituitary insulin-like growth factor system. Endocrinology 1992;131:2588–2594.
19.
Oomizu S, Takeuchi S, Takahashi S: Stimulatory effect of insulin-like growth factor I on proliferation of mouse pituitary cells in serum-free culture. J Endocrinol 1998;157:53–62.
20.
Wynick D, Small CJ, Bacon A, Holmes FE, Norman M, Ormandy CJ, Kilic E, Kerr NC, Ghatei M, Talamantes F, Bloom SR, Pachnis V: Galanin regulates prolactin release and lactotroph proliferation. Proc Natl Acad Sci USA 1998;95:12671–12676.
21.
Hentges S, Boyadjieva N, Sarkar DK: Transforming growth factor-β3 stimulates lactotrope cell growth by increasing basic fibroblast growth factor from folliculo-stellate cells. Endocrinology 2000;141:859–867.
22.
Sharma S, Oomizu S, Kakeya T, Masui T, Takeuchi S, Takahashi S: Gene expression and the physiological role of transforming growth factor-α in the mouse pituitary. Zool Sci 2003;20:83–89.
23.
Hentges S, Pastorcic M, De A, Boyadjieva N, Sarkar DK: Opposing actions of two transforming growth factor-β isoforms on anterior lactotropic cell proliferation. Endocrinology 2000;141:1528–1535.
24.
Takahashi S, Kawashima S: Age-related changes in prolactin cell percentage and serum prolactin levels in intact and neonatally gonadectomized male and female rats. Acta Anat 1982;113:211–217.
25.
Sasaki F, Iwama Y: Sex difference in prolactin and growth hormone cells in mouse adenohypophysis: Stereological, morphometric, and immunohistochemical studies by light and electron microscopy. Endocrinology 1988;123:905–912.
26.
Chen HT: Postnatal development of pituitary lactotropes in the rat measured by reverse hemolytic plaque assay. Endocrinology 1987;120:247–253.
27.
Ellerkmann E, Nagy GM, Frawley LS: Rapid augmentation of prolactin cell number and secretory capacity by an estrogen-induced factor released from the neurointermediate lobe. Endocrinology 1991;129:838–842.
28.
Schafer M, Reiner J, Geis R, Voigt KH, Martin R: Co-occurrence of immunoreactive corticotropin-like and α-melanotropin-like material in pituitary cells: Differences between young and adult rats. Neuropeptides 1983;3:387–397.
29.
Tanaka S, Kurosumi K: Differential subcellular localization of ACTH and α-MSH in corticotropes of the rat anterior pituitary. Cell Tissue Res 1986;243:229–238.
30.
Lindley SE, Gunnet JW, Lookingland KJ, Moore KE: Effects of alterations in the activity of tuberohypophysial dopaminergic neurons on the secretion of α-melanocyte stimulating hormone. Proc Soc Exp Biol Med 1988;188:282–286.
31.
Goudreau JL, Lindley SE, Lookingland KJ, Moore KE: Evidence that hypothalamic periventricular dopamine neurons innervate the intermediate lobe of the rat pituitary. Neuroendocrinology 1992;56:100–105.
32.
Goudreau JL, Falls WM, Lookingland KJ, Moore KE: Periventricular-hypophysial dopaminergic neurons innervate the intermediate but not the neural lobe of the rat pituitary gland. Neuroendocrinology 1995;62:147–154.
33.
Escalada J, Cacicedo L, Ortego J, Melian E, Sanchez-Franco F: Prolactin gene expression and secretion during pregnancy and lactation in the rat: Role of dopamine and vasoactive intestinal peptide. Endocrinology 1996;137:631–637.
34.
Watanabe H, Yoneda M: Evaluation of the role of melanocortin-3 and -4 receptors in leptin stimulated and spontaneous growth hormone secretion in rats. Neuroendocrinology 2003;78:331–338.
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