Comparison of oestrogen and GnRH agonist analogue-induced inhibition of the pituitary-testicular function in rat.

Abstract

The purpose of the present study was to compare the inhibitory effects of oestrogen and a gonadotrophin releasing hormone agonist analogue (GnRH-A) on the pituitary-testicular function of adult rats. Animals were treated with sc injections of oestrogen (diethylstilboestrol, DES, 5 or 50 micrograms/kg body weight/day) or a gonadotrophin releasing hormone agonist analogue. [(D-Ser-(tBu)6)des-Gly10-GnRH N-ethylamide, GnRH-A, 0.4 or 4 micrograms/kg/day] up to 12 days. Serum LH (24 h after the last hormone injection) decreased by 83% in 3 days with DES, but was unchanged during 12 days of GnRH-A treatment. Serum testosterone (T) decreased by 98% during DES treatment, and also clearly but less profoundly, by 89% with GnRH-A. Maximal decrease in the weights of the ventral prostate and seminal vesicles were 73-78% with DES-treatment, but clearly slower, and to a lesser extent, with GnRH-A (33-41%). Testicular weights decreased consistently (up to 41%) with GnRH-A treatment only. DES decreased the content of testicular LH receptors by 40% in 12 days whereas GnRH-A caused a loss of 97% in LH binding. Testicular lactogen receptors decreased to similar extents (by 68-78%) with both treatments. A clear increase in serum progesterone/T ratio was observed with both types of treatment, suggesting blockade of steroidogenesis at the C21 steroid level. These findings suggest that the antigonadal actions of oestrogen in the intact animal are largely due to a decrease of circulating gonadotrophin levels, and that those of GnRH-A are predominately due to Leydig cell LH-receptor down-regulation and steroidogenic lesions, induced by transiently elevated gonadotrophin levels. The inhibitory effects of oestrogen on testicular function appeared to be faster and more complete that those of GnRH-A in the present short-term experiments.