Endocrinology, Vol 129, 3299-3304, Copyright © 1991 by Endocrine Society

ARTICLES

In vivo regulation of FSH synthesis by inhibin and activin

RS Carroll, PM Kowash, JA Lofgren, RH Schwall and WW Chin
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

The effect of a single sc injection of the gonadal peptide, recombinant human activin A (rhActivin A), on gonadotropin synthesis and secretion was examined in adult and immature male and female rats and the effect of recombinant human inhibin A (rhInhibin A) was examined in adult male rats. Pituitary FSH beta, LH beta and alpha messenger RNA (mRNA) levels were determined by blot hybridization. Trunk blood was collected to measure serum FSH levels. Treatment with rhInhibin A (100 micrograms/kg) resulted in a decrease in FSH beta mRNA to 2% of controls levels 6 h after injection. FSH beta mRNA levels started to rebound at 10 h, but were still significantly lower than vehicle- treated controls. Serum FSH levels were significantly reduced at 2 h and were reduced further at 6 and 10 h. There were no significant changes in alpha and LH beta mRNA levels. RhActivin A, at the highest dose (500 micrograms/kg), in immature male rats had only a modest effect (1.2- and 1.3-fold increase) on FSH beta mRNA levels and FSH secretion, respectively, at 2 h. No increase in FSH synthesis and FSH secretion was observed in adult male rats. In contrast, both immature and adult-ovariectomized E2 implanted females showed a robust response to rhActivin A. In immature females, 2 h after rhActivin A (100 and 500 micrograms/kg) administration, FSH beta mRNA levels were elevated 2.0- and 2.2-fold. At this time serum FSH was also elevated. At 6 and 10 h rhActivin A significantly reduced FSH beta mRNA levels from vehicle- treated controls. In contrast, FSH secretion was elevated at 6 h and returned to baseline at 10 h. Administration of rhActivin A (500 micrograms/kg) to adult, ovariectomized-E2 females resulted in a significant increase in FSH beta mRNA levels and FSH secretion at 2 and 6 h. There were no significant changes in alpha and LH beta mRNA levels in either males or females. Thus, these in vivo studies have shown that rhInhibin A can inhibit FSH beta mRNA levels and FSH secretion in the adult male rat. RhActivin A stimulates FSH synthesis and secretion in the immature and adult ovariectomized-E2 females, but has little or no effect in immature and adult males. Hence, there is a sexual dimorphic response to rhActivin A in vivo in the rat.

This article has been cited by other articles:

				J. P. Moore ,Jr. and S. J. Winters Weaning and the Developmental Changes in Follicle-Stimulating Hormone, Pituitary Adenylate Cyclase-Activating Polypeptide, and Inhibin B in the Male Rat Biol Reprod, April 1, 2008; 78(4): 752 - 760. [Abstract] [Full Text] [PDF]

				J. M Young, J. L Juengel, K. G Dodds, M. Laird, P. K Dearden, A. S McNeilly, K. P McNatty, and T. Wilson The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures J. Endocrinol., February 1, 2008; 196(2): 251 - 261. [Abstract] [Full Text] [PDF]

				J. L. Kipp, S. M. Kilen, T. K. Woodruff, and K. E. Mayo Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary J. Biol. Chem., December 14, 2007; 282(50): 36755 - 36765. [Abstract] [Full Text] [PDF]

				J. L. Kipp, S. M. Kilen, S. Bristol-Gould, T. K. Woodruff, and K. E. Mayo Neonatal Exposure to Estrogens Suppresses Activin Expression and Signaling in the Mouse Ovary Endocrinology, May 1, 2007; 148(5): 1968 - 1976. [Abstract] [Full Text] [PDF]

				D. S. Perrien, N. S. Akel, P. K. Edwards, A. A. Carver, M. S. Bendre, F. L. Swain, R. A. Skinner, W. R. Hogue, K. M. Nicks, T. M. Pierson, et al. Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength Endocrinology, April 1, 2007; 148(4): 1654 - 1665. [Abstract] [Full Text] [PDF]

				S. J. Gregory, C. T. Lacza, A. A. Detz, S. Xu, L. A. Petrillo, and U. B. Kaiser Synergy between Activin A and Gonadotropin-Releasing Hormone in Transcriptional Activation of the Rat Follicle-Stimulating Hormone-{beta} Gene Mol. Endocrinol., January 1, 2005; 19(1): 237 - 254. [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]

				J. S. Bailey, N. Rave-Harel, S. M. McGillivray, D. Coss, and P. L. Mellon Activin Regulation of the Follicle-Stimulating Hormone {beta}-Subunit Gene Involves Smads and the TALE Homeodomain Proteins Pbx1 and Prep1 Mol. Endocrinol., May 1, 2004; 18(5): 1158 - 1170. [Abstract] [Full Text] [PDF]

				S. B. R. Jacobs, D. Coss, S. M. McGillivray, and P. L. Mellon Nuclear Factor Y and Steroidogenic Factor 1 Physically and Functionally Interact to Contribute to Cell-Specific Expression of the Mouse Follicle-Stimulating Hormone-{beta} Gene Mol. Endocrinol., August 1, 2003; 17(8): 1470 - 1483. [Abstract] [Full Text] [PDF]

				H.-J. Huang, J. Sebastian, B. D. Strahl, J. C. Wu, and W. L. Miller Transcriptional Regulation of the Ovine Follicle-Stimulating Hormone-{beta} Gene by Activin and Gonadotropin-Releasing Hormone (GnRH): Involvement of Two Proximal Activator Protein-1 Sites for GnRH Stimulation Endocrinology, June 1, 2001; 142(6): 2267 - 2274. [Abstract] [Full Text] [PDF]

				A.J. Tilbrook, D.M. de Kretser, and I.J. Clarke Influence of the Degree of Stimulation of the Pituitary by Gonadotropin-Releasing Hormone on the Action of Inhibin and Testosterone to Suppress the Secretion of the Gonadotropins in Rams Biol Reprod, February 1, 2001; 64(2): 473 - 481. [Abstract] [Full Text]

				C. Molter-Gérard, J. Fontaine, S. Guérin, and C. Taragnat Differential Regulation of the Gonadotropin Storage Pattern by Gonadotropin-Releasing Hormone Pulse Frequency in the Ewe Biol Reprod, May 1, 1999; 60(5): 1224 - 1230. [Abstract] [Full Text]

				M. Safi, N. Buys, O.M. Onagbesan, B. Vleugels, and E. Decuypere Quantification of Inhibin/Activin {alpha} and ßA Subunit Messenger Ribonucleic Acid by Competitive Reverse Transcription-Polymerase Chain Reaction in Chicken Granulosa Cells during Follicular Development Biol Reprod, November 1, 1998; 59(5): 1047 - 1054. [Abstract] [Full Text]

				S. Ramaswamy, C. R. Pohl, A. S. McNeilly, S. J. Winters, and T. M. Plant The Time Course of Follicle-Stimulating Hormone Suppression by Recombinant Human Inhibin A in the Adult Male Rhesus Monkey (Macaca mulatta) Endocrinology, August 1, 1998; 139(8): 3409 - 3415. [Abstract] [Full Text] [PDF]

				A.-M. Andersson, A. Juul, J. H. Petersen, J. Muller, N. P. Groome, and N. E. Skakkebak Serum Inhibin B in Healthy Pubertal and Adolescent Boys: Relation to Age, Stage of Puberty, and Follicle-Stimulating Hormone, Luteinizing Hormone, Testosterone, and Estradiol Levels J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3976 - 3981. [Abstract] [Full Text] [PDF]