Androgens regulate circulating levels of insulin-like growth factor (IGF)-I and IGF binding protein-3 during puberty in male baboons.

Abstract

To examine the role of androgens in initiating the pubertal rise in circulating insulin-like factor-I (IGF-I) levels, a longitudinal study of puberty in 13 male hamadryas baboons was conducted over 3 yr. The five control baboons commenced puberty (initial testicular enlargement) at a mean +/- SE age of 4.2 +/- 0.4 yr. Another eight baboons were castrated prepubertally; of those four received testosterone pellets (dose equivalent: 12.5-50 mg every 6 weeks) implanted se from the time of puberty. Body weight, crown-rump length, and limb length measurements, synchronized to pubertal onset, suggest that a pubertal growth spurt occurs in male baboons. Control baboons had a marked rise (4- to 5-fold; P < 0.0001) in circulating IGF-I levels; maximum IGF-I levels (168 +/- 9 nmol/L) were reached 42 months after the onset of puberty (mean chronological age 7.5 yr). Castrated baboons had no significant rise in IGF-I levels, however, administration of testosterone resulted in a close approximation of the normal pubertal rise in IGF-I (maximum values 140 +/- 8 nmol/L), confirmed by comparison of fitted sigmoid curves (r2 > 0.99; chronological age ED50 controls, 4.4 +/- 0.1 yr and castrate + testosterone, 4.3 +/- 0.1 yr). Serum IGF binding protein-3 levels paralleled the rise in IGF-I consistent with a common regulatory mechanism. In another study, castration of four sexually mature male baboons aged 11.12 +/- 1.16 yr had no effect on serum IGF-I levels (P = 0.5). This indicates that androgens are the predominant determinant of circulating IGF-I in the male baboon, and that this is an uniquely pubertal phenomenon.