Endocrinology, Vol 125, 2127-2133, Copyright © 1989 by Endocrine Society

ARTICLES

Insulin and insulin-like growth factor-I stimulate the 3 beta- hydroxysteroid dehydrogenase activity of human placental cytotrophoblasts

JE Nestler
Division of Endocrinology and Metabolism, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.

The placenta is the primary source of progesterone during pregnancy. Because pregnant diabetic women are reported to have higher serum progesterone levels than nondiabetic pregnant women, we studied the roles of insulin and insulin-like growth factor-I (IGF-I) in the regulation of human cytotrophoblastic 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity. Incubation of cytotrophoblasts with insulin or IGF-I for 24 h significantly increased the ability of these cells to convert pregnenolone to progesterone by 75.8 +/- 16.5% (+/- SE) and 65.4 +/- 12.7%, respectively. Treatment with either insulin or IGF-I did not alter cytotrophoblastic production of 20 alpha- hydroxypregn-4-en-3-one (the primary metabolite of progesterone), thus demonstrating that these peptides increased progesterone synthesis (i.e. 3 beta HSD activity) rather than decreased progesterone catabolism. Insulin and IGF-I stimulated 3 beta HSD activity at concentrations as low as 50 and 10 ng/ml, respectively. Insulin- and IGF-I-stimulated 3 beta HSD activities were completely inhibited by concurrent treatment with either actinomycin-D or cycloheximide, suggesting that new mRNA and protein synthesis are required for these peptides to exert their effects. Blockade of the IGF-I receptor of cytotrophoblasts with alpha IR-3, a monoclonal anti-IGF-I receptor antibody, prevented the stimulation of 3 beta HSD activity by IGF-I, but did not alter insulin's stimulatory effect. Thus, the two hormones can each stimulate 3 beta HSD activity via activation of their respective receptors. These studies indicate that insulin and IGF-I can regulate human cytotrophoblastic 3 beta HSD activity in vitro. Since pregnant diabetic women manifest peripheral hyperinsulinemia, and IGF-I levels in fetal cord sera from diabetic pregnancies may be elevated, these observations may help explain the elevated serum progesterone levels associated with pregnancy in the diabetic patient.

This article has been cited by other articles:

				N. Xita and A. Tsatsoulis Fetal Programming of Polycystic Ovary Syndrome by Androgen Excess: Evidence from Experimental, Clinical, and Genetic Association Studies J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1660 - 1666. [Abstract] [Full Text] [PDF]

				J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]

				T. Sir-Petermann, M. Maliqueo, B. Angel, H.E. Lara, F. Perez-Bravo, and S.E. Recabarren Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization Hum. Reprod., October 1, 2002; 17(10): 2573 - 2579. [Abstract] [Full Text] [PDF]

				G. J. Reid, A. S. Flozak, and R. A. Simmons Placental Expression of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor in the Growth-Restricted Fetal Rat Reproductive Sciences, July 1, 2002; 9(4): 210 - 214. [Abstract] [PDF]

				C. Menaa, F.ço. Vrtovsnik, Gér. Friedlander, M. Corvol, and M.èl. Garabédian Insulin-like Growth Factor I, a Unique Calcium-dependent Stimulator of 1,25-Dihydroxyvitamin D(3) Production J. Biol. Chem., October 27, 1995; 270(43): 25461 - 25467. [Abstract] [Full Text] [PDF]