Endocrinology, Vol 122, 1603-1612, Copyright © 1988 by Endocrine Society

ARTICLES

Somatomedin-C/insulin-like growth factor I as an enhancer of androgen biosynthesis by cultured rat ovarian cells

ER Hernandez, CE Resnick, ME Svoboda, JJ Van Wyk, DW Payne and EY Adashi
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.

The ovarian granulosa cell has recently been shown to be a site of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) production, reception, and action. These observations have generally been interpreted to suggest the existence of an autocrine loop concerned with granulosa cell physiology. It is the objective of the in vitro studies reported herein to extend these observations by evaluating the interaction of Sm-C/IGF-I with the adjacent thecal-interstitial cell. Treatment of collagenase-processed whole ovarian dispersates or highly enriched (greater than 90%) thecal-interstitial cells from immature rats with Sm-C/IGF-I (50 ng/ml) or hCG (1 ng/ml), resulted in 2.1- and 4.0-fold increments in the accumulation of androsterone (3 alpha- hydroxy-5 alpha-androstane-17-one), the main androgenic steroid identified in culture media. However, combined treatment with both agents unmasked a synergistic interaction producing a 3.3-fold increase in the hCG-stimulated accumulation of androsterone, an effect consequent to enhanced androgen biosynthesis rather than diminished degradation. Unaccounted for by an increase in viable ovarian cell numbers and independent of the hCG dose (0.1-10 ng/ml) used, the Sm- C/IGF-I effect proved time and dose dependent, with a projected minimal effective dose of 3 ng/ml and a minimal time requirement of 72 h. [125I]Iodo-Sm-C/IGF-I binding to untreated highly enriched thecal- interstitial cells proved saturable, with a single class (Hill coefficient = 0.98 +/- 0.01) of high affinity (Kd = 3.0 nM), low capacity (maximum binding = 10,840 +/- 2,108 sites/cell) binding sites. Limited specificity studies using related peptides produced a rank order of competitive potency of: Sm-C/IGF-I greater than multiplication stimulating activity greater than insulin, a pattern compatible with the presence of type I IGF receptors. Other related peptides, such as porcine proinsulin and porcine desoctapeptide insulin, proved weakly effective in inhibiting Sm-C/IGF-I binding to its receptor; unrelated peptides such as porcine relaxin and erythropoietin were without effect. Taken together, these findings suggest that 1) the thecal- interstitial cell, like the granulosa cell, may be a site of Sm-C/IGF-I reception and action, and 2) the ability of high dose insulin to stimulate ovarian androgen biosynthesis may be due to its capacity to act as a Sm-C/IGF-I surrogate, its high dose requirements reflecting cross-interaction with the type I receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				X. Li, Y. Dai, and W.R. Allen Influence of Insulin-Like Growth Factor-I on Cytoplasmic Maturation of Horse Oocytes In Vitro and Organization of the First Cell Cycle Following Nuclear Transfer and Parthenogenesis Biol Reprod, October 1, 2004; 71(4): 1391 - 1396. [Abstract] [Full Text] [PDF]

				V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]

				G. Carneiro, P. Lorenzo, C. Pimentel, L. Pegoraro, M. Bertolini, B. Ball, G. Anderson, and I. Liu Influence of Insulin-Like Growth Factor-I and Its Interaction with Gonadotropins, Estradiol, and Fetal Calf Serum on In Vitro Maturation and Parthenogenic Development in Equine Oocytes Biol Reprod, March 1, 2001; 65(3): 899 - 905. [Abstract] [Full Text] [PDF]

				L. Falsetti, A. Gambera, and G. Tisi Efficacy of the combination ethinyl oestradiol and cyproterone acetate on endocrine, clinical and ultrasonographic profile in polycystic ovarian syndrome Hum. Reprod., January 1, 2001; 16(1): 36 - 42. [Abstract] [Full Text] [PDF]

				E. R. Hernandez Embryo implantation and GnRH antagonists: Embryo implantation: the Rubicon for GnRH antagonists Hum. Reprod., June 1, 2000; 15(6): 1211 - 1216. [Abstract] [Full Text] [PDF]

				A. E. Taylor, J. Hubbard, and E. J. Anderson Impact of Binge Eating on Metabolic and Leptin Dynamics in Normal Young Women J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 428 - 434. [Abstract] [Full Text]

				S. Kol, I. Ben-Shlomo, M. Ando, D. W. Payne, and E. Y. Adashi Interleukin-1{beta} Stimulates Ovarian Phospholipase A2 (PLA2) Expression and Activity: Up-Regulation of Both Secretory and Cytosolic PLA2 Endocrinology, January 1, 1997; 138(1): 314 - 321. [Abstract] [Full Text] [PDF]

				J. B. Miller and C. Obasiolu The Effect of Insulin and Insulin-Like Growth Factors on Luteal Progesterone Secretion in the Rabbit Reproductive Sciences, September 1, 1996; 3(5): 262 - 266. [Abstract] [PDF]

				D. W. Payne, C. Shackleton, H. Toms, I. Ben-Shlomo, S. Kol, M. deMoura, J. F. Strauss, and E. Y. Adashi A Novel Nonhepatic Hydroxycholesterol 7alpha-Hydroxylase That Is Markedly Stimulated by Interleukin-1beta J. Biol. Chem., August 11, 1995; 270(32): 18888 - 18896. [Abstract] [Full Text] [PDF]