EFFECTS OF PITUITARY-GONADAL SUPPRESSION WITH A GONADOTROPIN-RELEASING-HORMONE AGONIST ON FETAL GONADOTROPIN-SECRETION, FETAL GONADAL DEVELOPMENT AND MATERNAL STEROID-SECRETION IN THE SHEEP

In order to investigate the regulation of the hypothalamopituitary-gon adal axis during fetal development, sheep fetuses at day 70 of gestati on were implanted subcutaneously with a biodegradable implant containi ng the long-acting gonadotrophin-releasing hormone (GnRH) agonist, bus erelin. The treatment of fetuses with a GnRH agonist throughout the la st half of gestation (term=145 days) abolished the increase in plasma LH concentrations that was seen in 2-day-old control lambs in response to an injection of GnRH. This attenuated response was associated with corresponding reductions in the pituitary content of LH and FSH. Immu nolocalization studies revealed that pituitary glands from newborn lam bs implanted with a GnRH agonist during fetal development were devoid of immunopositive LH- and FSH-containing cells. At birth the testicula r weights of GnRH agonist-treated ram lambs were significantly decreas ed by 40% when compared with controls. This was associated with a 45% reduction in the total number of Sertoli cells per testis. In newborn ewe lambs GnRH agonist treatment had no effect on ovarian weight or on the morphological appearance of the ovaries. GnRH agonist treatment h ad no effect on the plasma concentrations of progesterone and oestrone in the maternal circulation or on the length of gestation. These resu lts show (1) that GnRH positively regulates the synthesis and secretio n of gonadotrophins in the fetus, (2) that reduced fetal gonadotrophic support during the last half of gestation results in a reduction in t esticular growth, and (3) that fetal gonadotrophins do not affect mate rnal steroid secretion.