Steroidogenic Enzyme Gene Expression in Androgen Induced Polycystic Ovaries in the Rabbit

Autor: Songya Pang, K.-Y. F. Pau, Harold G. Spies, Jose R. Manaligod, Kotaro Iwamoto, J. Ian Mason
Rok vydání: 2001
Předmět:
Zdroj: Clinical Pediatric Endocrinology. 10:17-28
ISSN: 1347-7358
0918-5739
DOI: 10.1297/cpe.10.17
Popis: We investigated ovarian steroidogenic enzyme gene expression in exogenous androgen induced polycystic ovaries (PCO) in rabbits. Twelve 3-month peripubertal, and seven 9-11 month reproductive aged New Zealand White female rabbits were divided into four treatment (Rx) groups: controls receiving saline only, testosterone (T) treated (6-10 mg/Rx), LHRH analog (L) treated (leuprolide depot 1.0-1.2 mg/Rx), and T plus L treated (T+L). Animals in each group were administered the treatment IM every 2 to 3 weeks for 12-14 weeks. Serum T levels (every 1-3 wks) in T (127 ± 29 ng/dl) and T+L treated (144 ± 27 ng/dl) groups during the treatment period were unequivocally higher than the levels in controls (16 ± 6 ng/dl) and L treatment (22 ± 4 ng/dl) groups. Serum E2, LH and FSH levels (every 1-3 wks) showed no discernable differences between the groups. Microscopic examination of the L, T+L and T treated rabbit ovaries revealed a spectrum of PCO changes in comparison to the age-matched control ovaries, depicting marked interstitial hypercellularity and large cystic follicles in all except markedly decreased immature follicles and a few small cystic follicles in T treated peripubertal rabbits. Ovarian P450 cholesterol side-chain cleavage (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA and protein levels in PCOs of T and T + L treated animals were similar to the age-matched control ovaries, while in L treated PCOs both P450scc and 3β-HSD mRNA and protein levels were increased. Thus excess T alone did not alter the ovarian steroidogenic enzyme gene expressions despite the morphology changes. The L treatment alone had a gonadotropin agonistic effect resulting in both PCO and increased ovarian steroidogenic enzyme gene expression. However, excess T abolished the L-mediated increased ovarian steroidogenic enzyme gene expression, indicating the presence of an inhibitory effect of T on L induced ovarian steroidogenic enzyme gene expression. These findings suggest that the pathogenic mechanism by which PCO is induced by extra-ovarian source of T differs from that induced by increased gonadotropic effect alone.
Databáze: OpenAIRE