This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bachelot, A. Articles by Binart, N. Search for Related Content PubMed PubMed Citation Articles by Bachelot, A. Articles by Binart, N.

Growth Hormone Is Required for Ovarian Follicular Growth

Molecular Endocrinology, INSERM U-44 (A.B., P.I.B., P.A.K., N.B.), 75730 Paris, France; UMR 6073, INRA (P.M.), 37380 Nouzilly, France; and Edison Biotechnology Institute, Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University (K.C., J.J.K.), Athens, Ohio 45701

Address all correspondence and requests for reprints to: Dr. Nadine Binart, INSERM, U-344, Endocrinologie Moléculaire, Facultéde Médecine Necker, 156 rue de Vaugirard, 75730 Paris, France. E-mail: binart{at}necker.fr.

To analyze the consequences of the absence of GH receptor (GHR) and GH-binding protein (GHBP) on female reproductive function, we used a mouse model in which the GHR/GHBP gene has been disrupted by homologous recombination. The major effect on reproductive function seen in GHR/GHBP knockout (KO) compared with wild-type animals is a dramatic decrease in litter size; this defect is due to a reduction of the ovulation rate. The ovulatory response to exogenous gonadotropin treatment is also 3-fold reduced in GHR/GHBP KO compared with the wild-type ovaries. These results establish that the reduced rate of ovulation is essentially due to an ovarian defect rather than a deficiency in pituitary gonadotropins. The number of follicles per ovary is markedly reduced, although all categories of follicles are represented. Interestingly, the number of healthy follicles from antral and preovulatory stages is dramatically decreased in GHR/GHBP KO in comparison with wild-type follicles. The capacity of follicles to bind LH, FSH, and IGF-I was not diminished. IGF-I treatment using micropumps is not able to rescue either fertility or ovarian responsiveness to exogenous gonadotropins, suggesting that the effect of GH is independent of IGF-I. In conclusion, these results indicate that the reduction of litter size in GHR/GHBP KO mice is the consequence of an alteration of the growth of follicles and suggest that the effects of GH effects on follicular growth are independent of IGF-I.

This article has been cited by other articles:

				E.M. Kolibianakis, C.A. Venetis, K. Diedrich, B.C. Tarlatzis, and G. Griesinger Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis Hum. Reprod. Update, June 26, 2009; (2009) dmp026v1. [Abstract] [Full Text] [PDF]

				K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws Ovarian follicle development and transgenic mouse models Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555. [Abstract] [Full Text] [PDF]

				K. A Slot, J. Kastelijn, A. Bachelot, P. A Kelly, N. Binart, and K. J Teerds Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice. Reproduction, March 1, 2006; 131(3): 525 - 532. [Abstract] [Full Text] [PDF]

				J. Tesarik, A. Hazout, and C. Mendoza Improvement of delivery and live birth rates after ICSI in women aged >40 years by ovarian co-stimulation with growth hormone Hum. Reprod., September 1, 2005; 20(9): 2536 - 2541. [Abstract] [Full Text] [PDF]

				Y. Guo, Y. Lu, D. Houle, K. Robertson, Z. Tang, J. J. Kopchick, Y. L. Liu, and J.-L. Liu Pancreatic Islet-Specific Expression of an Insulin-Like Growth Factor-I Transgene Compensates Islet Cell Growth in Growth Hormone Receptor Gene-Deficient Mice Endocrinology, June 1, 2005; 146(6): 2602 - 2609. [Abstract] [Full Text] [PDF]

				I. Y. Lebedeva, V. A. Lebedev, R. Grossmann, T. I. Kuzmina, and N. Parvizi Characterization of Growth Hormone Binding Sites in Granulosa and Theca Layers at Different Stages of Follicular Maturation and Ovulatory Cycle in the Domestic Hen Biol Reprod, October 1, 2004; 71(4): 1174 - 1181. [Abstract] [Full Text] [PDF]

				V. Chandrashekar, D. Zaczek, and A. Bartke The Consequences of Altered Somatotropic System on Reproduction Biol Reprod, July 1, 2004; 71(1): 17 - 27. [Abstract] [Full Text] [PDF]

				N. Scanlan, L. Dufourny, and D. C. Skinner Somatostatin-14 Neurons in the Ovine Hypothalamus: Colocalization with Estrogen Receptor {alpha} and Somatostatin-28(1-12) Immunoreactivity, and Activation in Response to Estradiol Biol Reprod, October 1, 2003; 69(4): 1318 - 1324. [Abstract] [Full Text] [PDF]