Predominant Suppression of Follicle-Stimulating Hormone β-Immunoreactivity after Long-Term Treatment of Intact and Castrate Adult Male Rats with the Gonadotrophin-Releasing Hormone Agonist Deslorelin

Journal of Neuroendocrinology

Volumn 24, Issue 5, 2012, Pages 737-747

  Smith, A W ^a   Asa, C S ^b   Edwards, B S ^a   Murdoch, W J ^a   Skinner, D C ^a  

^a UNIVERSITY OF WYOMING   (United States)

^b SAINT LOUIS ZOO   (United States)

Author keywords

Contraception; FSH; GnRH; Gonadotrophins; LH; Testosterone

Indexed keywords

CHORIONIC GONADOTROPIN ALPHA SUBUNIT; DESLORELIN; FOLLITROPIN BETA SUBUNIT; LUTEINIZING HORMONE BETA SUBUNIT; TESTOSTERONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CASTRATED MALE; CELL POPULATION; CONTROLLED STUDY; GONADOTROPIN SECRETING CELL; IMMUNE DEFICIENCY; IMMUNOCYTOCHEMISTRY; IMMUNOREACTIVITY; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; SPRAGUE DAWLEY RAT; TESTIS WEIGHT;

ANIMALS; DOWN-REGULATION; FOLLICLE STIMULATING HORMONE; GONADOTROPHS; GONADOTROPIN-RELEASING HORMONE; HORMONE ANTAGONISTS; IMMUNOHISTOCHEMISTRY; MALE; ORCHIECTOMY; ORGAN SIZE; PITUITARY GLAND; RATS; RATS, SPRAGUE-DAWLEY; TESTIS; TIME FACTORS; TRIPTORELIN PAMOATE;

EID: 84859887397     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/j.1365-2826.2011.02271.x     Document Type: Article

References (101)

1. Kher R, Kalla NR. Antifertility effects of an LHRH agonist in male mice. Contraception 1996; 53: 299-306.
2. Labrie F, Auclair C, Cusan L, Kelly PA, Pelletier G, Ferland L. Inhibitory effect of LHRH and its agonists on testicular gonadotropin receptors and spermatogenesis in the rat. Int J Androl Suppl 1978; 2: 303-318.
3. Trigg TE, Wright PJ, Armour AF, Williamson PE, Junaidi A, Martin GB, Doyle AG, Walsh J. Use of a GnRH analogue implant to produce reversible long-term suppression of reproductive function in male and female domestic dogs. J Reprod Fertil Suppl 2001; 57: 255-261.
4. Resko JA, Belanger A, Labrie F. Effect of chronic treatment with a potent luteinizing hormone releasing hormone agonist on serum luteinizing hormone and steroid levels in the male rhesus monkey. Biol Reprod 1982; 26: 378-384.
5. Lincoln GA, Fraser HM, Abbott MP. Blockade of pulsatile LH, FSH and testosterone secretion in rams by constant infusion of an LHRH agonist. J Reprod Fertil 1986; 77: 587-597.
6. Tilbrook AJ, Galloway DB, Williams AH, Clarke IJ. Treatment of young rams with an agonist of GnRH delays reproductive development. Horm Behav 1993; 27: 5-28.
7. Eymann J, Herbert CA, Thomson BP, Trigg TE, Cooper DW, Eckery DC. Effects of deslorelin implants on reproduction in the common brushtail possum (Trichosurus vulpecula). Reprod Fertil Dev 2007; 19: 899-909.
8. Lincoln GA. Long-term stimulatory effects of a continuous infusion of LHRH agonist on testicular function in male red deer (Cervus elaphus). J Reprod Fertil 1987; 80: 257-261.
9. Herbert CA, Trigg TE, Renfree MB, Shaw G, Eckery DC, Cooper DW. Effects of a gonadotropin-releasing hormone agonist implant on reproduction in a male marsupial, Macropus eugenii. Biol Reprod 2004; 70: 1836-1842.
10. Aspden WJ, Rao A, Rose K, Scott PT, Clarke IJ, Trigg TE, Walsh J, D'Occhio MJ. Differential responses in anterior pituitary luteinizing hormone (LH) content and LH b- and a-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin. Domest Anim Endocrinol 1997; 14: 429-437.
11. Aspden WJ, van Reenen N, Whyte TR, Maclellan LJ, Scott PT, Trigg TE, Walsh J, D'Occhio MJ. Increased testosterone secretion in bulls treated with a luteinizing hormone releasing hormone (LHRH) agonist requires endogenous LH but not LHRH. Domest Anim Endocrinol 1997; 14: 421-428.
12. Labrie F, Belanger A, Luu-The V, Labrie C, Simard J, Cusan L, Gomez J, Candas B. Gonadotropin-releasing hormone agonists in the treatment of prostate cancer. Endocr Rev 2005; 26: 361-379.
13. Shally AV. Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides 1999; 20: 1247-1262.
14. Schally AV, Redding TW, Comaru-Shally AM. Potential use of analogs of luteinizing hormone-releasing hormone in the treatment of hormone-sensitive neoplasmas. Cancer Treat Rep 1984; 68: 281-289.
15. Smith MR. Androgen deprivation therapy for prostate cancer: new concepts and concerns. Curr Opin Endocrinol Diabetes Obes 2007; 14: 247-254.
16. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxypreogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod 2006; 21: 248-256.
17. Rackow BW, Arici A. Options for medical treatment of myomas. Obstet Gynecol Clin North Am 2006; 33: 97-113.
18. Badaru A, Wilson DM, Bachrach LK, Fechner P, Gandrud LM, Durham E, Wintergerst K, Chi C, Klein KO, Neely EK. Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty. J Clin Endocrinol Metab 2006; 91: 1862-1867.
19. Bowen RL, Verdile G, Liu T, Parlow AF, Perry G, Smith MA, Martins RN, Atwood CS. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-β precursor protein and amyloid-β deposition. J Biol Chem 2004; 279: 20539-20545.
20. Mathias JR, Clench MH, Reeves-Darby VG. Effects of leuprolide acetate in patients with functional bowel disease. Long-term follow-up after double-blind, placebo-controlled study. Dig Dis Sci 1994; 39: 1163-1170.
21. Setji TL, Brown AJ. Comprehensive clinical management of polycystic ovary syndrome. Minerva Med 2007; 98: 175-189.
22. Clowse ME, Behera MA, Anders CK, Copland S, Coffman CJ, Leppert PC, Bastian LA. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health 2009; 18: 311-319.
23. Hazum E, Cuatrecasas P, Marian J, Conn PM. Receptor-mediated internalization of fluorescent gonadotropin-releasing hormone by pituitary gonadotropes. Proc Natl Acad Sci USA 1980; 77: 6692-6695.
24. Conn PM, Huckle WR, Andrews WV, McArdle CA. The molecular mechanism of action of gonadotropin releasing hormone (GnRH) in the pituitary. Rec Prog Horm Res 1987; 43: 29-68.
25. Smith MA, Perrin MH, Vale WV. Desensitization of cultured pituitary cells to gonadotropin-releasing hormone: evidence for a post-receptor mechanism. Mol Cell Endocrinol 1983; 30: 85-96.
26. Crowder ME, Herring RD, Nett TM. Rapid recovery of gonadotroph function after down-regulation of receptors for GnRH in ewes. J Reprod Fertil 1986; 78: 577-585.
27. Counis R, Garrel G, Laverriere J, Simon V, Bleux C, Magre S, Cohen-Tannoudji J. The GnRH receptor and the response of gonadotrope cells to GnRH pulse frquency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization. Folia Histochem Cytobiol 2009; 47: S81-S87.
28. Horvath JE, Bajo AM, Schally AV, Kovacs M, Herbert F, Groot K. Effects of long-term treatment with the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl and the LHRH antagonist Cetrorelix on the levels of pituitary LHRH receptors and their mRNA expression in rats. Proc Natl Acad Sci USA 2002; 99: 15048-15053.
29. Huhtaniemi I, White R, McArdle CA, Persson BE. Will GnRH antagonists improve prostate cancer treatment? Trends Endocrinol Metab 2009; 20: 43-50.
30. Pawson AJ, Faccenda E, Maudsley S, Lu Z-L, Naor Z, Millar RP. Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology 2008; 149: 1415-1422.
31. McArdle CA, Forrest-Owen W, Willars GB, Davidson J, Poch A, Kratzmeier M. Desensitization of gonadotropin-releasing hormone action in the gonadotrope-deprived alpha T3-1 cell line. Endocrinology 1995; 136: 4864-4871.
32. Willars GB, Challiss RA, Nahorski SR. Acute regulation of the receptor-mediated phosphoinositide signal transduction pathway. J Lipid Mediat Cell Signal 1996; 14: 157-168.
33. 2+ responses in alpha T3-1 gonadotropes. J Biol Chem 2001; 276: 3123-3129.
34. Rolandi E, Franceschini R, Giberti C, Brancadoro T, Martorana G, Barreca T. Sustained impairment of pituitary and testicular function in prostatic cancer patients treated with a depot form of a GnRH agonist. Horm Res 1988; 30: 22-25.
35. Hall MC, Fritzsch RJ, Sagalowsky AI, Ahrens A, Petty B, Roehrborn CG. Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer. Urology 1999; 53: 898-902.
36. Kaku H, Saika T, Tsushima T, Ebara S, Senoh T, Yamato T, Nasu Y, Kumon H. Time course of serum testosterone and luteinizing hormone levels after cessation of long-term luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer. Prostate 2006; 66: 439-444.
37. Nejat RJ, Rashid HH, Bagiella E, Katz AE, Benson MC. A prospective analysis of time to normalization of serum testosterone after withdrawal of androgen deprivation therapy. J Urol 2000; 164: 1891-1894.
38. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360: 103-106.
39. Oefelein MG. Time to normalization of serum testosterone after 3-month luteinizing hormone-releasing hormone agonist administered in the neoadjuvant setting: implications for dosing schedule and neoadjuvant study consideration. J Urol 1998; 160: 1685-1688.
40. Sandow J, von Rechenberg W, Baeder C, Engelbart K. Antirfertility effects of an LH-RH analogue in male rats and dogs. Int J Fertil 1980; 25: 213-221.
41. McNeilly JR, Brown P, Clark AJ, McNeilly AS. Gonadotrophin-releasing hormone modulation of gonadotrophins in the ewe: evidence for differential effects on gene expression and hormone secretion. J Mol Endocrinol 1991; 7: 35-43.
42. Rodin DA, Lalloz MRA, CLayton RN. Gonadotropin-releasing hormone regulates follicle-stimulating hormone beta-subunit gene expression in the male rat. Endocrinology 1989; 125: 1282-1289.
43. Lalloz MRA, Detta A, CLayton RN. Gonadotropin-releasing hormone desensitization preferentially inhibits expression of the luteinizing hormon b-subunit gene in vivo. Endocrinology 1988; 122: 1689-1694.
44. Wormald PJ, Abrahamson MJ, Millar RP. Culture of functionally active human pituitary cells: investigation of gonadotropin regulation. J Clin Endocrinol Metab 1988; 66: 1272-1277.
45. Song J, Kost CK Jr, Martin DS. Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway. Cardiovasc Res 2006; 72: 456-463.
46. Periti P, Mazzei T, Mini E. Clinical pharmacokinetics of depot leuprorelin. Clin Pharmacokinet 2002; 41: 485-504.
47. Sartor O, Dineen MK, Perez-Marreno R, Chu FM, Carron GJ, Tyler RC. An eight-month clinical study of LA-2575 30.0mg: a new 4-month, subcutaneous delivery system for leuprolide acetate in the treatment of prostate cancer. Urology 2003; 62: 319-323.
48. Conn PM, Crowley WF Jr. Gonadotropin-releasing hormone and its analogues. N Engl J Med 1991; 324: 93-103.
49. Stefanini M, De Martino C, Zamboni L. Fixation of ejaculated spermatozoa for electron microscopy. Nature 1967; 216: 173-174.
50. Dada MO, Campbell GT, Blake CA. The localization of gonadotrophs in normal adult male and female rats. Endocrinology 1984; 114: 397-406.
51. Hunter WM, Greenwood FC. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 1962; 194: 495-496.
52. Taragnat C, Bernier A, Fontaine J. Gonadotrophin storage patterns in the ewe during the oestrous cycle or after long-term treatment with a GnRH agonist. J Endocrinol 1998; 156: 149-157.
53. Hirsch HJ, Gillis D, Strich D, Chertin B, Farkas A, Lindenberg T, Gelber H, Spitz IM. The histrelin implant: a novel treatment for central precocious puberty. Pediatrics 2005; 116: e798-e802.
54. Lahlou N, Carel JC, Chaussain JL, Roger M. Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab 2000; 13(Suppl 1): 723-737.
55. Klibanski A, Jameson JL, Biller BM, Crowley WF Jr, Zervas NT, Rivier J, Vale WW, Bikkal H. Gonadotropin and a-subunit responses to chronic gonadotropin-releasing hormone analog administration in patients with glycoprotein hormone-secreting pituitary tumors. J Clin Endocrinol Metab 1989; 68: 81-86.
56. Hirsch HJ, Lahlou N, Gillis D, Strich D, Rosenberg-Hagen B, Chertin B, Farkas A, Hartman H, Spitz IM. Free α-subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the histrelin implant. J Clin Endocrinol Metab 2010; 95: 2841-2844.
57. Kanasaki H, Purwana IN, Mijiddorj T, Oride A, Miyazaki K. Possible involvement of PACAP and PACAP type 1 receptor in GnRH-induced FSH beta-subunit gene expression. Regul Pept 2011; 167: 227-232.
58. Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM. GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Mol Endocrinol 2009; 23: 1022-1032.
59. Hart GR, Gowing H, Burrin JM. Effects of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, on pituitary hormone release in rats. J Endocrinol 1992; 134: 33-41.
60. Culler MD, Paschall CS. Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates the gonadotropin-releasing activity of luteinizing hormone-releasing hormone. Endocrinology 1991; 129: 2260-2262.
61. Winters SJ, Tsujii T, Attardi B. Effects of GnRH and PACAP on gonadotropin secretion and subunit messenger RNAs. Ann NY Acad Sci 1996; 805: 343-352.
62. Winters SJ, Dalkin AC, Tsujii T. Evidence that pituitary adenylate cyclase activating polypeptide suppresses follicle-stimulating hormone-beta messenger ribonucleic acid levels by stimulating follistatin gene transcription. Endocrinology 1997; 138: 4324-4329.
63. Winters S, Ghooray D, Fujii Y, Moore J, Nevitt J, Kakar S. Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. Mol Cell Endo 2007; 271: 45-54.
64. Kawakami S, Fujii Y, Okada Y, Winters SJ. Paracrine regulation of FSH by follistatin in folliculostellate cell-enriched primate pituitary cell cultures. Endocrinology 2002; 143: 2250-2258.
65. Oride A, Kanasaki H, Purwana IN, Mutiara S, Miyazaki K. Follistatin, induced by thyrotropin-releasing hormone (TRH), plays no role in prolactin expression but affects gonadotropin FSHb expression as a paracrine factor in pituitary somatolactotroph GH3 cells. Regul Pept 2009; 156: 65-71.
66. Meistrich ML, Wilson DM, Porter KL, Huhtaniemi I, Shetty G, Shuttlesworth GA. Restoration of spermatogenesis in dibromochloropropane (DBCP)-treated rats by hormone suppression. Toxical Sci 2003; 76: 418-426.
67. Kangasniemi M, Wilson G, Huhtaniemi I, Meistrich ML. Protection against procarbazine-induced testicular damage by GnRH-agonist and antiandrogen treatment in the rat. Endocrinology 1995; 136: 3677-3680.
68. Cusan L, Auclair C, Belanger A, Ferland L, Kelly PA, Seguin C, Labrie F. Inhibitory effects of long term treatment with a luteinizing hormone-releasing hormone agonist on the pituitary-gonadal axis in male and female rats. Endocrinology 1979; 104: 1369-1376.
69. Padula AM. GnRH analogues-agonists and antagonists. Anim Reprod Sci 2005; 88: 115-126.
70. 102 of the gonadotropin-releasing hormone receptor is a critical determinant of potency for agonists containing C-terminal glycinamide. J Biol Chem 1996; 271: 15510-15514.
71. Barrell GK, Schaafsma SCT, Ridgway MJ, Wellby M, Miller LA. Effects of a synthetic gonadotrophin-releasing hormone agonist, leuprolide, on rut-associated events in male red deer. Anim Prod Sci 2009; 49: 1120-1124.
72. Aspden WJ, Rao A, Scott PT, Clarke IJ, Trigg TE, Walsh J, D'Occhio MJ. Direct actions of the luteinizing hormone-releasing hormone agonist, deslorelin, on anterior pituitary contents of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH and FSH subunit messenger ribonucleic acid, and plasma concentrations of LH and FSH in castrated male cattle. Biol Reprod 1996; 55: 386-392.
73. van der Kaay DC, de Jong FH, Rose SR, Odink RJ, Bakker-van Waarde WM, Sulkers EJ, Hokken-Koelega AC. Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age. Horm Res 2009; 71: 260-267.
74. Lerrant Y, Kottler M, Bergametti M, Moumni M, Blumberg-Tick J, Counis R. Expression of gonadotropin-releasing hormone (GnRH) receptor gene is altered by GnRH agonist densensitization in a manner similar to that of gonadotropin b-subunit genes in normal and castrated rat pituitary. Endocrinology 1995; 136: 2803-2808.
75. Nadji M. Quantitative immunohistochemistry of estrogen receptor in breast cancer: 'much ado about nothing!'. Appl Immunohistochem Mol Morphol 2008; 16: 105-107.
76. Leong AS. Quantitation in immunohistology: fact or fiction? A discussion of variables that influence results. Appl Immunohistochem Mol Morphol 2004; 12: 1-7.
77. Kitahara K, Sakai Y, Hosaka M, Hira Y, Kakizaki H, Watanabe T. Effects of a depot formulation of the GnRH agonist leuprorelin on the ultrastructure of male rat pituitary gonadotropes. Arch Histol Cytol 2007; 70: 79-93.
78. McNeilly AS, Crawford JL, Taragnat C, Nicol L, McNeilly JR. The differential secretion of FSH and LH: regulation through genes, feedback and packaging. Reprod Suppl 2003; 61: 463-476.
79. Abbot SD, Docherty K, Roberts JL, Tepper MA, Chin WW, Clayton RN. Castration increases luteinizing hormone subunit messenger RNA levels in male rat pituitaries. J Endocrinol 1985; 107: R1-R4.
80. Nolan LA, Levy A. A population of non-luteinising hormone/non-adrenocorticotrophic hormone-positive cells in the male rat anterior pituitary responds mitotically to both gonadectomy and adrenalectomy. J Neuroendocrinol 2006; 18: 655-661.
81. Sun YT, Irby DC, Robertson DM, de Kretser DM. The effects of exogenously administered testosterone on spermatogenesis in intact and hypophysectomized rats. Endocrinology 1989; 125: 1000-1010.
82. Pelletier G, Cusan L, Auclair C, Kelly PA, Désy L, Labrie F. Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, Des-Gly-NH210] LHRH ethylamide. Endocrinology 1978; 103: 641-643.
83. Ward JA, Furr BJ, Valcaccia B, Curry B, Bardin CW, Gunsalus GL, Morris ID. Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist. J Androl 1989; 10: 478-486.
84. Lamminen T, Jokinen P, Jiang M, Pakarinen P, Simonsen H, Huhtaniemi I. Human FSH b subunit gene is highly conserved. Mol Hum Reprod 2005; 11: 601-605.
85. Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 1997; 15: 201-204.
86. Abel MH, Wootton AN, Wilkins V, Huhtaniemi I, Knight PG, Charlton HM. The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology 2000; 141: 1795-1803.
87. Bahk JY, Hyun JS, Chung SH, Lee H, Kim MO, Lee BH, Choi WS. Stage specific identification of the expression of GnRH mRNA and localization of the GnRH receptor in mature rat and adult human testis. J Urol 1995; 154: 1958-1961.
88. Clayton RN, Katikineni M, Chan V, Dufau ML, Catt KJ. Direct inhibition of testicular function by gonadotropin-releasing hormone: mediation by specific gonadotropin-releasing hormone receptors in interstitial cells. Proc Natl Acad Sci USA 1980; 77: 4459-4463.
89. Stojilkovic SS. Calcium signalling systems. Compr Physiol 2011. Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology: 177-224. First published in print 1988. doi:
90. Yao B, Liu HY, Gu YC, Shi SS, Tao XQ, Li XJ, Ge YF, Cui YX, Yang GB. Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells. Asian J Androl 2011; 13: 438-445.
91. Lefebvre F, Belanger A, Pelletier G, Labrie F. Recovery of gonadal functions in the adult male rat following cessation of five-month daily treatment with an LHRH agonist. J Androl 1984; 5: 181-192.
92. Wierman ME, Wang C. Androgen selectively stimulates follicle-stimulating hormone-beta mRNA levels after gonadotropin-releasing hormone antagonist administration. Biol Reprod 1990; 42: 563-571.
93. Paul SJ, Ortolano GA, Haisenleder DJ, Stewart JM, Shupnik MA, Marshall JC. Gonadotropin subunit messenger RNA concentrations after blockade of gonadotropin-releasing hormone action: testosterone selectively increases follicle-stimulating hormone b-subunit messenger RNA by posttranscriptional mechanisms. Mol Endocrinol 1990; 4: 1943-1955.
94. Winters SJ, Ishizaka K, Kitahara S, Troen P, Attardi B. Effects of testosterone on gonadotropin subunit messenger ribonucleic acids in the presence or absence of gonadotropin-releasing hormone. Endocrinology 1992; 130: 726-734.
95. Leal AM, Blount AL, Donaldson CJ, Bilezikjian LM, Vale WW. Regulation of follicle-stimulating hormone secretion by the interactions of activin-A, dexamethasone and testosterone in anterior pituitary cell cultures of male rats. Neuroendocrinology 2003; 77: 298-304.
96. Bilezikjian LM, Corrigan AZ, Blount AL, Vale WW. Pituitary follistatin and inhibin subunit messenger ribonucleic acid levels are differentially regulated by local and hormonal factors. Endocrinology 1996; 137: 4277-4284.
97. Sharma N, Marzo SJ, Jones KJ, Foecking EM. Electrical stimulation and testosterone differentially enhance expression of regeneration-associated genes. Exp Neurol 2010; 223: 183-191.
98. Shuto Y, Somogyvari-Vigh A, Onda H, Arimura A. Effect of hypophysectomy on pituitary adenylate cyclase activating polypeptide gene expression in the rat hypothalamus. Peptides 1995; 16: 407-413.
99. Thackray VG, Mellon PL, Coss D. Hormones in synergy: regulation of the pituitary gonadotropin genes. Mol Cell Endocrinol 2010; 314: 192-203.
100. Thackray VG, Mellon PL. Synergistic induction of follicle-stimulating hormone b-subunit gene expression by gonadal steroid hormone receptors and Smad proteins. Endocrinology 2008; 149: 1091-1102.
101. Song K, Wang H, Krebs TL, Wang B, Kelley TJ, Danielpour D. DHT selectively reverses Smad3-mediated/TGF-b-induced responses through transcriptional down-regulation of Smad3 in prostate epithelial cells. Mol Endocrinol 2010; 24: 2019-2029.