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In order to investigate the regulation of the hypothalamo-pituitary-gonadal axis during fetal development, sheep fetuses at day 70 of gestation were implanted subcutaneously with a biodegradable implant containing the longacting gonadotrophin-releasing hormone (GnRH) agonist, buserelin. The treatment of fetuses with a GnRH agonist throughout the last 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. Immunolocalization studies revealed that pituitary glands from newborn lambs implanted with a GnRH agonist during fetal development were devoid of immunopositive LH- and FSH-containing cells. At birth the testicular weights of GnRH agonist-treated ram lambs were significantly decreased 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 had no effect on the plasma concentrations of progesterone and oestrone in the maternal circulation or on the length of gestation. These results show (1) that GnRH positively regulates the synthesis and secretion of gonadotrophins in the fetus, (2) that reduced fetal gonadotrophic support during the last half of gestation results in a reduction in testicular growth, and (3) that fetal gonadotrophins do not affect maternal steroid secretion.

Journal of Endocrinology (1994) 141, 317–324