Pubertal augmentation in juvenile rhesus monkey testosterone production induced by invariant gonadotropin stimulation is inhibited by estrogen.
BACKGROUND
Experimental and epidemiological studies have indicated the adverse impact of changing estrogen [17beta-estradiol (E2)] milieu or of endocrine disrupters on testis development and function.


OBJECTIVE
This study examines the direct impact of elevated E2 levels on gonadotropin-induced pubertal testis development and function in the primate.


METHODS
Juvenile monkeys, which have characteristically little endogenous gonadotropin secretion, were treated with pulsatile infusions of recombinant monkey (rm) FSH (rmFSH) and LH (rmLH) in the presence (experiment 1, approximately 100 pg/ml for about 15-20 wk; experiment 2, approximately 400 pg/ml for about 5 wk) or absence (control group) of elevated E2 in the circulation. Changes in circulating concentrations of E2, gonadotropins, testosterone (T), and inhibin B were monitored throughout the study. The number of Leydig cells per testis was determined after immunohistochemical staining for 3-beta hydroxysteroid dehydrogenase in experiment 2.


RESULTS
Exogenous gonadotropin treatment produced physiological, episodic, and similar circulating concentrations of FSH and LH in both groups. Exposure to approximately 100 pg/ml of E2 appeared to blunt testicular T production. Exposure to approximately 400 pg/ml of E2 led to a significant (approximately 75%) inhibition of T production together with a marked (approximately 40%) decrease in Leydig cell numbers per testis and a notable inhibition in the growth of the testis. In contrast, E2 exposure had little effect on inhibin B production.


CONCLUSIONS
The direct testicular impact of elevated E2 is on Leydig cell number, T production, and testicular growth, but not on inhibin B production. This experimental paradigm provides a powerful primate model for the examination of the direct impact of E2 or other endocrine disrupters on pubertal testicular development.
Ramaswamy
S
S
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, S-831A, Scaife Hall, Pittsburgh, Pennsylvania 15260, USA. sramas@pitt.edu
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D004958:Estradiol / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood; D007150:Immunohistochemistry; D007265:Inhibins / Q000096:biosynthesis; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*
D006062:Gonadotropins; D011994:Recombinant Proteins; C422364:inhibin B; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015067:17-Hydroxysteroid Dehydrogenases