ANDROGEN REGULATION OF CIRCULATING INSULIN-LIKE GROWTH FACTOR-I DURING PUBERTY IN MALE HYPOGONADAL MICE

This study aimed at determining the relationship of sex steroids, part icularly in the perinatal period, to the pubertal insulin-like growth factor-I (IGF-I) surge in male mice. We used hypogonadal (hpg) mice, w hich have a major deletion in the gonadotrophin-releasing hormone (GnR H) gene, in order to have a model lacking all GnRH-induced gonadotroph in and sex steroid secretion throughout pre- and postnatal life. Cross -sectional data on body weights and weights of testes, seminal vesicle s, kidneys, liver and spleen from 9 to 77 days of age were obtained in male hpg, heterozygous (Hz) and homozygous normal (N/N) littermates ( n=75-78/group). These data did not reveal any difference between Hz an d N/N mice. Hpg mice had decreased body weights which by 70-77 days of age were approximately 18% less than normal controls. Testes and semi nal vesicles of hpg mice did not demonstrate any significant postnatal growth. Relative to body weight, kidney weights were also markedly re duced in hpg mice (P<0.0001), deviating significantly from normal by 2 8-35 days of age, reflecting the impact of androgen deficiency on a no n-reproductive organ. From the cross-sectional data it was concluded t hat puberty commenced soon after weaning (21 days) in the male and tha t maturity was achieved within 4-5 weeks. Longitudinal study showed th at, compared with normal controls, untreated hpg mice had an exaggerat ed pubertal IGF-I surge (P<0.05) which peaked in mid-puberty. This, to gether with their reduced body weights (P<0.05), were normalized by tr eatment from 21 to 70 days of age with two 1 cm s.c. implants of testo sterone (n=6) or dihydrotestosterone (n=7). There was no difference in IGF-I levels or in weights of testes, seminal vesicles, kidney, liver or spleen between testosterone and dihydrotestosterone treatments (P> 0.05). Prolonged high levels of androgen also restored testicular and seminal vesicle weights to 40% of phenotypically normal controls, whil e kidney, liver and spleen weights were also significantly increased. The pubertal IGF-I surge in mice does not, therefore, require androgen s in either the pre- or postnatal periods, and it is exaggerated in an drogen-deficient male mice and dampened to normal regardless of aromat ization.