ROLE OF GNRH IN THE ONTOGENY AND REGULATION OF THE FETAL HYPOTHALAMO-PITUITARY-GONADAL AXIS IN SHEEP

Adult reproductive ability is to a large extent determined by the appr opriate development of the reproductive axis during fetal life. Studie s have investigated the role of the fetal hypothalamus in the ontogeny and regulation of pituitary gonadal function during fetal development in sheep. Using immunocytochemistry, we examined the ontogeny of gona dotroph development in the pituitary of female sheep fetuses. At day 7 0 of gestation (term = 145 days), only immunopositive LH beta cells we re present. The number and intensity of staining of these LH beta cell s had increased by day 100 but had declined again by day 130. Immunopo sitive alpha-subunit and FSH beta cells appeared at day 100 of gestati on and had further increased in number and staining intensity by day 1 30 of gestation. Treatment of fetuses with the GnRH agonist buserelin resulted in desensitization of the fetal pituitary gonadotrophs, inhib ition of pituitary LH beta and FSH beta mRNA expression and a reductio n in the number of immunopositive gonadotrophin-containing cells. Puls atile GnRH treatment resulted in pituitary-gonadal activation and an i ncrease in LH, FSH and testosterone secretion in males. Thus, the synt hesis and secretion of the gonadotrophins during fetal development is critically dependent on the secretion of GnRH from the fetal hypothala mus. Inhibition of fetal gonadotrophins by buserelin treatment from da y 70 of gestation resulted in a 40% reduction in the size of the fetal testis at birth, and there were no effects on the fetal ovaries. This reduction in testis size was due to a 45% reduction in the number of Sertoli cells. However, when buserelin was given between day 70 and da y 110 of gestation, there were no effects on testis size or morphologi cal development of the testis, suggesting that gonadotrophins regulate testicular development during:a 'critical window' late in gestation. Taken together, these studies provide convincing evidence that GnRH pl ays a central role in the ontogeny and regulation of pituitary-gonadal function during fetal life.