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(MS26) GENETIC MODELS FOR HORMONAL REGULATION OF SPERMATOGENESIS. Allan, Charles1, Handelsman, David1, 1 ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia ABSTRACT- Genetic mouse models have now been developed to investigate selective deficiency of hormone ligands or receptors at every level of the hypothalamic-pituitary-gonadal axis. The gonadotropin-deficient hypogonadal (hpg) mouse provides a valuable experimental platform to study specific hormone contributions to male germ cell development, which is arrested at meiosis. Our laboratory has selectively examined FSH and androgen actions on the dormant undeveloped but hormonally-responsive hpg testis. Transgenic FSH dose-dependently restored hpg Sertoli cell numbers to normal in the absence of LH, a finding complemented by normal Sertoli numbers in LHR-null testes. Although promoting normal Sertoli cell number, FSH activity alone supported half of normal mitotic and meiotic germ cell development, plus limited and incomplete post-meiotic progression. In comparison, testosterone or hCG treatment produced a small but significant increase (approximately 40%) in hpg Sertoli cell numbers without FSH; an effect which occurred beyond the normal perinatal period of Sertoli cell expansion. Testosterone or hCG also stimulated half of normal meiosis, plus the completion of spermiogenesis and fertility in hpg males. The hpg background was also used to evaluate the activity of transgenic mutated (Asp567Gly) or wildtype human FSH receptor expressed in FSH-deficient males, which provided strong in vivo evidence that this mutation activates ligand-independent and FSH-like signalling in Sertoli cells. Comparison of our findings with other genetic mouse models allows a detailed dissection of FSH and androgen actions during testicular development and function. KEY WORDS: FSH, mouse, spermatogenesis, androgen |
