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Androgen regulation of circulating insulin-like growth factor-I during puberty in male hypogonadal mice



Androgen regulation of circulating insulin-like growth factor-I during puberty in male hypogonadal mice



Journal of Endocrinology 139(1): 57-65



This study aimed at determining the relationship of sex steroids, particularly in the perinatal period, to the pubertal insulin-like growth factor-I (IGF-I) surge in male mice. We used hypogonadal (hpg) mice, which have a major deletion in the gonadotrophin-releasing hormone (GnRH) gene, in order to have a model lacking all GnRH-induced gonadotrophin and sex steroid secretion throughout pre- and postnatal life. Cross-sectional data on body weights and weights of testes, seminal vesicles, 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 and 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 seminal vesicles of hpg mice did not demonstrate any significant postnatal growth. Relative to body weight, kidney weights were also markedly reduced in hpg mice (P lt 0.0001), deviating significantly from normal by 28-35 days of age, reflecting the impact of androgen deficiency on a non-reproductive organ. From the cross-sectional data it was concluded that puberty commenced soon after weaning (21 days) in the male and that maturity was achieved within 4-5 weeks. Longitudinal study showed that, compared with normal controls, untreated hpg mice had an exaggerated pubertal IGF-I surge (P lt 0.005) which peaked in mid-puberty. This, together with their reduced body weights (P lt 0.05), were normalized by treatment from 21 to 70 days of age with two 1 cm s.c. implants of testosterone (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 gt 0.05). Prolonged high levels of androgen also restored testicular and seminal vesicle weights to 40% of phenotypically normal controls, while kidney, liver and spleen weights were also significantly increased. The pubertal IGF-I surge in mice does not, therefore, require androgens in either the pre- or postnatal periods, and it is exaggerated in androgen-deficient male mice and dampened to normal regardless of aromatization.

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Accession: 002301370

Download citation: RISBibTeXText

PMID: 8254294

DOI: 10.1677/joe.0.1390057



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