The pattern of growth hormone (GH) secretion is sexually dimorphic in rats. We have previously shown that the secretory pattern in adult ovariectomized (OVX) female rats is masculinized by the administration of a single dose of dihydrotestosterone (DHT), a nonaromatizable androgen. To investigate the primary site of action of DHT in the brain, a small amount of DHT was injected directly into a defined area of the brain, and the blood GH profile was observed for 18 h in conscious adult OVX female rats. The bilateral direct injection of 1 µg DHT into the medial preoptic area (MPA) produced a male-like secretory pattern of GH in OVX rats. The masculinizing effects became apparent at 9 h after injection, from which time the episodic GH secretion was produced regularly at intervals of about 150 min, the amplitude of the peak increased and baseline levels were lowered. These parameters, analyzed during 9–18 h after DHT injection, were not different from those in adult male rats. On the contrary, microinjection of DHT into the bed nucleus of the stria terminalis, the hypothalamic periventricular nucleus, or the hypothalamic arcuate-ventromedial nucleus did not affect the secretory pattern of GH. The data indicate that DHT primarily acts on cells in the MPA through androgen receptors and modulates the secretion of somatostatin and/or GH-releasing hormone secondarily to masculinize the GH secretory pattern in OVX rats.

1.
Tannenbaum GS, Martin JB: Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 1976;98:562–570.
2.
Tannenbaum GS, Ling N: The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 1984;115:1952–1957.
3.
Clark RG, Chambers G, Lewin J, Robinson ICAF: Automated repetitive microsampling of blood: Growth hormone profiles in conscious male rats. J Endocrinol 1986;111:27–35.
4.
Clark RG, Carlsson LMS, Robinson ICAF: Growth hormone secretory profiles in conscious female rats. J Endocrinol 1987;114:399–407.
5.
Eden S: Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 1979;105:555–560.
6.
Jansson JO, Eden S, Isaksson OGP: Sexual dimorphism in the control of growth hormone secretion. Endocr Rev 1986;6:128–150.
7.
Gabriel SM, Roncancio JR, Ruiz NS: Growth hormone pulsatility and the endocrine milieu during sexual maturation in male and female rats. Neuroendocrinology 1992;56:619–625.
8.
Jansson JO, Frohman LA: Differential effects of neonatal and adult androgen exposure on the growth hormone secretory pattern in male rats. Endocrinology 1987;120:1551–1557.
9.
Jansson JO, Frohman LA: Inhibitory effect of the ovaries on neonatal androgen imprinting of growth hormone secretion in female rats. Endocrinology 1987;121:1417–1423.
10.
Painson JC, Thorner MO, Krieg RJ, Tannenbaum GS: Short-term adult exposure to estradiol feminizes the male pattern of spontaneous and growth hormone-releasing factor-stimulated growth hormone secretion in the rat. Endocrinology 1992;130:511–519.
11.
Tamura H, Sugihara H, Kamegai J, Minami S, Wakabayashi I: Masculinizing effect of dihydrotestosterone on growth hormone secretion is inhibited in ovariectomized rats with anterolateral deafferentation of the medial basal hypothalamus or in intact female rats. J Neuroendocrinol 2000;12:369–375.
12.
Plotsky PM, Vale W: Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. Science 1985;230:461–463.
13.
Sugihara H, Minami S, Wakabayashi I: Post-somatostatin rebound secretion of growth hormone is dependent on growth hormone-releasing factor in unrestrained female rats. J Endocrinol 1989;122:583–591.
14.
Akira S, Wakabayashi I, Sugihara H, Minami S, Takahashi F, Motoyama A: Effect of testosterone on growth hormone secretion in female rats during a continuous infusion of growth hormone-releasing factor. Neuroendocrinology 1988;47:116–124.
15.
Werner H, Koch Y, Baldino F, Gozes I: Steroid regulation of somatostatin mRNA in the rat hypothalamus. J Biol Chem 1988;263:7666–7671.
16.
Zorrilla R, Simard J, Rheaume E, Labrie F, Pelletier G: Multihormonal control of pre-pro-somatostatin mRNA levels in the periventricular nucleus of the male and female rat hypothalamus. Neuroendocrinology 1990;52:527–536.
17.
Argente J, Chowen-Breed JA, Steiner RA, Clifton DK: Somatostatin messenger RNA in hypothalamic neurons is increased by testosterone through activation of androgen receptors and not by aromatization to estradiol. Neuroendocrinology 1990;52:342–349.
18.
Simonian SX, Murray HE, Gillies GE, Herbison AE: Estrogen-dependent ontogeny of sex differences in somatostatin neurons of the hypothalamic periventricular nucleus. Endocrinology 1998;139:1420–1428.
19.
Millard WJ, Politch JA, Martin JB, Fox TO: Growth hormone-secretory patterns in androgen-resistant (testicular feminized) rats. Endocrinology 1986;119:2655–2660.
20.
Hasegawa O, Sugihara H, Minami S, Wakabayashi I: Masculinization of growth hormone (GH) secretory pattern by dihydrotestosterone is associated with augmentation of hypothalamic somatostatin and GH-releasing hormone mRNA levels in ovariectomized adult rats. Peptides 1992;13:475–481.
21.
Handa RJ, Roselli CE, Horton L, Resko JA: The quantitative distribution of cytosolic androgen receptors in microdissected areas of the male rat brain: Effects of estrogen treatment. Endocrinology 1987;121:233–240.
22.
Roselli CE, Handa RJ, Resko JA: Quantitative distribution of nuclear androgen receptors in microdissected areas of the rat brain. Neuroendocrinology 1989;49:449–453.
23.
Simerly RB, Chang C, Muramatsu M, Swanson LW: Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: An in situ hybridization study. J Comp Neurol 1990;294:76–95.
24.
McAbee MD, DonCarlos LL: Ontogeny of region-specific sex differences in androgen receptor messenger ribonucleic acid expression in the rat forebrain. Endocrinology 1998;139:1738–1745.
25.
Bingaman EW, Baeckman LM, Yracheta JM, Handa RJ, Thackery SG: Localization of androgen receptor within peptidergic neurons of the rat forebrain. Brain Res Bull 1994;35:379–382.
26.
Huang X, Harlan RE: Androgen receptor immunoreactivity in somatostatin neurons of the periventricular nucleus but not in the bed nucleus of the stria terminalis in male rats. Brain Res 1994;652:291–296.
27.
Herbison AE: Sexually dimorphic expression of androgen receptor immunoreactivity by somatostatin neurones in rat hypothalamic periventricular nucleus and bed nucleus of the stria terminalis. J Neuroendocrinol 1995;7:543–553.
28.
Minami S, Suzuki N, Sugihara H, Tamura H, Emoto N, Wakabayashi I: Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats. J Endocrinol 1997;153:283–290.
29.
Merriam GR, Wachter KW: Algorithms for the study of episodic hormone secretion. Am J Physiol 1982;243:E310–E318.
30.
Okada K, Sugihara H, Minami S, Wakabayashi I: Effect of parenteral administration of selected nutrients and central injection of γ-globulin from antiserum to neuropeptide Y on growth hormone secretory pattern in food-deprived rats. Neuroendocrinology 1993;57:678–686.
31.
Simerly RB: Anatomical substrates of hypothalamic integration; in Paxinos G (ed): The Rat Nervous System. San Diego, Academic Press, 1995, pp 353–376.
32.
Karteszi M, Fiok J, Makara GB: Lack of episodic growth hormone secretion in rats with anterolateral deafferentation of the medial-basal hypothalamus. J Endocrinol 1982;94:77–81.
33.
Minami S, Wakabayashi I, Sugihara H, Kamegai J, Hasegawa O, Kitamura T, Yamada J: Effect of intermittent infusions of somatostatin on growth hormone secretion in unrestrained male rats with hypothalamic deafferentation. Brain Res 1990;509:293–298.
34.
Frohman LA, Downs TR, Katakami H, Jansson JO: The interaction of growth hormone-releasing hormone and somatostatin in the regulation of growth hormone secretion; in Issakson O, Binder C, Hall K, Hokfelt B (eds): Growth Hormone; Basic and Clinical Aspects. Proc 1st Nordisk Insulin Symposium. Amsterdam, Excerpta Media, 1987, pp 63–77.
35.
Dickson SL, Leng G, Robinson IC: Electrical stimulation of the rat periventricular nucleus influence the activity of hypothalamic arcuate neurones. J Neuroendocrinol 1994;6:359–367.
36.
Tannenbaum GS, Zhang WH, Lapointe M, Zeitler P, Beaudet A: Growth hormone-releasing hormone neurons in the arcuate nucleus express both sst1 and sst2 somatostatin receptor genes. Endocrinology 1998;139:1450–1453.
37.
Zhang WH, Beaudet A, Tannenbaum GS: Sexually dimorphic expression of sst1 and sst2 somatostatin receptor subtypes in the arcuate nucleus and anterior pituitary of adult rats. J Neuroendocrinol 1999;11:129–136.
38.
Bennett PA, Thomas GB, Howard AD, Feighner SD, Van der Ploeg LH, Smith RG, Robinson ICAF: Hypothalamic growth hormone secretagogue-receptor expression is regulated by growth hormone in the rats. Endocrinology 1997;138:4552–4557.
39.
Kamegai J, Wakabayashi I, Kineman RD, Frohman LA: Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats. J Neuroendocrinol 1999;11:299–306.
40.
Murray HE, Simonian SX, Herbison AE, Gillies GE: Ontogeny and sexual differentiation of somatostatin biosynthesis and secretion in the hypothalamic periventricular-median eminence pathway. J Neuroendocrinol 1999;11:35–42.
41.
Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I: Estrogen receptor (ER)α, but not ERβ, gene is expressed in growth hormone-releasing hormone neurons of the male rat hypothalamus. Endocrinology 2001;142:538–543.
42.
Lieberburg I, Maclusky NJ, McEwen BS: 5α-Dihydrotestosterone receptors in rat brain and pituitary cell nuclei. Endocrinology 1977;100:598–607.
43.
Roselli CE, Horton LE, Resko JA: Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system. Endocrinology 1985;117:2471–2477.
44.
Lephart ED: A review of brain aromatase cytochrome P450. Brain Res Rev 1996;22:1–26.
45.
Yamamoto KR: Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet 1985;19:209–252.
46.
McKenna NJ, Lanz RB, O’Malley BW: Nuclear receptor coregulators: Cellular and molecular biology. Endocr Rev 1999;20:321–344.
47.
Brann DW, Hendry LB, Mahesh VB: Emerging diversities in the mechanism of action of steroid hormones. J Steroid Biochem Mol Biol 1995;52:113–133.
48.
Murray HE, Gillies GE: Differential effects of neuroactive steroids on somatostatin and dopamine secretion from primary hypothalamic cell cultures. J Neuroendocrinol 1997;9:287–295.
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