Endocrinology, Vol 134, 1247-1253, Copyright © 1994 by Endocrine Society

ARTICLES

Dynamic regulation of pituitary follistatin messenger ribonucleic acids during the rat estrous cycle

LM Halvorson, J Weiss, AC Bauer-Dantoin and JL Jameson
Division of Reproductive Endocrinology, New England Medical Center, Boston, Massachusetts 02111.

FSH synthesis and secretion are regulated by a complex interplay of hypothalamic, gonadal, and pituitary factors. Recent evidence suggests that inhibin, activin, and follistatin, although originally identified as gonadal peptides, are also expressed in the pituitary, where they may be secreted and play an autocrine/paracrine role in the control of FSH beta gene expression. Attempts to study pituitary regulation of the genes encoding these proteins have been hampered by low levels of mRNA expression. Consequently, we developed quantitative reverse transcription-polymerase chain reaction assays for follistatin (FS) and the three subunits (alpha, beta A, and beta B) that comprise activin and inhibin. Expression of activin type II receptor (actRII) mRNA was also analyzed. Reasoning that mRNA levels of these FSH-regulating pituitary peptides might be modulated at times of increased FSH gene expression, two in vivo models were chosen for further investigation. 1) Two weeks after ovariectomy, rat pituitary FS mRNA levels increased substantially (4.09-fold vs. intact) with a modest increase in beta B- inhibin mRNA levels (1.88-fold vs. intact). No changes in alpha- inhibin, beta A-inhibin, or actRII mRNA levels were observed. 2) During the estrous cycle, pituitary FS gene expression varied strikingly, with a peak at 1800 h on proestrus (13.69-fold vs. 0900 h on proestrus), followed by a rapid decline at 2400 h on proestrus (2.10-fold vs. 0900 h on proestrus). A more detailed analysis of expression during proestrus revealed that peak FS mRNA levels preceded peak FSH beta gene expression by 6 h. Levels of the inhibin subunit and actRII transcripts varied minimally across the estrous cycle. We conclude that during the estrous cycle in rats, pituitary FS mRNA levels are regulated dynamically, whereas levels of inhibin/activin subunits and the activin receptor, actRII, very minimally. The observation that FS mRNA levels peak before maximal expression of FSH beta mRNA raises the possibility that FS facilitates, rather than inhibits, FSH biosynthesis in vivo.

This article has been cited by other articles:

				A. L. Blount, J. M. Vaughan, W. W. Vale, and L. M. Bilezikjian A Smad-binding Element in Intron 1 Participates in Activin-dependent Regulation of the Follistatin Gene J. Biol. Chem., March 14, 2008; 283(11): 7016 - 7026. [Abstract] [Full Text] [PDF]

				G. F Y Cheng, C.-W. Yuen, and W. Ge Evidence for the existence of a local activin follistatin negative feedback loop in the goldfish pituitary and its regulation by activin and gonadal steroids J. Endocrinol., December 1, 2007; 195(3): 373 - 384. [Abstract] [Full Text] [PDF]

				W. Zheng, M. Jimenez-Linan, B. S. Rubin, and L. M. Halvorson Anterior Pituitary Gene Expression with Reproductive Aging in the Female Rat Biol Reprod, June 1, 2007; 76(6): 1091 - 1102. [Abstract] [Full Text] [PDF]

				S. M. McGillivray, V. G. Thackray, D. Coss, and P. L. Mellon Activin and Glucocorticoids Synergistically Activate Follicle-Stimulating Hormone {beta}-Subunit Gene Expression in the Immortalized L{beta}T2 Gonadotrope Cell Line Endocrinology, February 1, 2007; 148(2): 762 - 773. [Abstract] [Full Text] [PDF]

				L. M Bilezikjian, A. L Blount, C. J Donaldson, and W. W Vale Pituitary actions of ligands of the TGF-{beta} family: activins and inhibins. Reproduction, August 1, 2006; 132(2): 207 - 215. [Abstract] [Full Text] [PDF]

				P. Lamba, M. M Santos, D. P Philips, and D. J Bernard Acute regulation of murine follicle-stimulating hormone {beta} subunit transcription by activin A J. Mol. Endocrinol., February 1, 2006; 36(1): 201 - 220. [Abstract] [Full Text] [PDF]

				T M Lovell, P G Knight, and R T Gladwell Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle J. Endocrinol., September 1, 2005; 186(3): 447 - 455. [Abstract] [Full Text] [PDF]

				J. P. Moore Jr, L. L. Burger, A. C. Dalkin, and S. J. Winters Pituitary Adenylate Cyclase Activating Polypeptide Messenger RNA in the Paraventricular Nucleus and Anterior Pituitary During the Rat Estrous Cycle Biol Reprod, September 1, 2005; 73(3): 491 - 499. [Abstract] [Full Text] [PDF]

				L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]

				K. A. Prendergast, L. L. Burger, K. W. Aylor, D. J. Haisenleder, A. C. Dalkin, and J. C. Marshall Pituitary Follistatin Gene Expression in Female Rats: Evidence That Inhibin Regulates Transcription Biol Reprod, February 1, 2004; 70(2): 364 - 370. [Abstract] [Full Text] [PDF]

				S. C. Chapman and T. K. Woodruff Betaglycan Localization in the Female Rat Pituitary: Implications for the Regulation of Follicle-Stimulating Hormone by Inhibin Endocrinology, December 1, 2003; 144(12): 5640 - 5649. [Abstract] [Full Text] [PDF]

				C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]

				M. Baratta, L.A. West, A.M. Turzillo, and T.M. Nett Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion of Follicle-Stimulating Hormone in Ovine Pituitary Cells Biol Reprod, February 1, 2001; 64(2): 714 - 719. [Abstract] [Full Text]

				B. L. Bohnsack, M. Szabo, S. M. Kilen, D. H.Y. Tam, and N. B. Schwartz Follistatin Suppresses Steroid-Enhanced Follicle-Stimulating Hormone Release In Vitro in Rats Biol Reprod, March 1, 2000; 62(3): 636 - 641. [Abstract] [Full Text]

				M. Szabo, S. M. Kilen, S. J. Nho, and N. B. Schwartz Progesterone Receptor A and B Messenger Ribonucleic Acid Levels in the Anterior Pituitary of Rats Are Regulated by Estrogen Biol Reprod, January 1, 2000; 62(1): 95 - 102. [Abstract] [Full Text]

				A. C. Dalkin, D. J. Haisenleder, J. T. Gilrain, K. Aylor, M. Yasin, and J. C. Marshall Gonadotropin-Releasing Hormone Regulation of Gonadotropin Subunit Gene Expression in Female Rats: Actions on Follicle-Stimulating Hormone {beta} Messenger Ribonucleic Acid (mRNA) Involve Differential Expression of Pituitary Activin ({beta}-B) and Follistatin mRNAs Endocrinology, February 1, 1999; 140(2): 903 - 908. [Abstract] [Full Text]

				M. E. Wilson and R. J. Handa Activin Subunit, Follistatin, and Activin Receptor Gene Expression in the Prepubertal Female Rat Pituitary Biol Reprod, August 1, 1998; 59(2): 278 - 283. [Abstract] [Full Text]

				A. C. Dalkin, D. J. Haisenleder, J. T. Gilrain, K. Aylor, M. Yasin, and J. C. Marshall Regulation of Pituitary Follistatin and Inhibin/Activin Subunit Messenger Ribonucleic Acids (mRNAs) in Male and Female Rats: Evidence for Inhibin Regulation of Follistatin mRNA in Females Endocrinology, June 1, 1998; 139(6): 2818 - 2823. [Abstract] [Full Text] [PDF]

				G. V. Childs and G. Unabia Cytochemical Studies of the Effects of Activin on Gonadotropin-releasing Hormone (GnRH) Binding by Pituitary Gonadotropes and Growth Hormone Cells J. Histochem. Cytochem., December 1, 1997; 45(12): 1603 - 1610. [Abstract] [Full Text] [PDF]

				S. J. Winters, A. C. Dalkin, and T. Tsujii Evidence That Pituitary Adenylate Cyclase Activating Polypeptide Suppresses Follicle-Stimulating Hormone-{beta} Messenger Ribonucleic Acid Levels by Stimulating Follistatin Gene Transcription Endocrinology, October 1, 1997; 138(10): 4324 - 4329. [Abstract] [Full Text] [PDF]

				G. V. Childs, B. T. Miller, and W. L. Miller Differential Effects of Inhibin on Gonadotropin Stores and Gonadotropin-Releasing Hormone Binding to Pituitary Cells from Cycling Female Rats Endocrinology, April 1, 1997; 138(4): 1577 - 1584. [Abstract] [Full Text] [PDF]