Transpubertal modulation of pituitary and testicular function in the ob/ob mouse

We have investigated developmental, transpubertal, changes in the responsiveness to stimulation of pituitary gland and testes from the male ob/ob mouse. These organs were removed from ob/ob mice at 33 and 90 days after birth and stimulated with GnRH and LH, respectively, in vitro. Pituitary glands from lean mice released significantly more LH than those from ob/ob mice at both ages. In contrast, FSH release was higher in young ob/ob mice but not significantly different at 90 days when compared with lean controls. LH-stimulated testes revealed that although the young ob/ob testes released significantly less testosterone (T) than lean controls, the response became normal after the time of expected puberty. The production of 5 alpha-androstane-3 alpha, 17 beta-diol (DIOL), although reduced at both ages in ob/ob mice, declined transpubertally in both lean and ob/ob mice. As a result, the ratio of T:DIOL which normally becomes much greater than 1 with the advent of puberty, also increases to greater than 1 in the ob/ob males, suggesting that sexual maturation of testicular androgen biosynthesis is approximately normal. We conclude that the differences in pituitary and testicular response to stimulation could arise from a defect in the ability of the pituitary gland to release gonadotrophins.