GROWTH-HORMONE (GH) REGULATION OF CIRCULATING INSULIN-LIKE GROWTH-FACTOR-I LEVELS DURING SEXUAL-MATURATION OF THE GH-DEFICIENT DWARF (DW DW) MALE-RAT/

In many mammalian species, circulating levels of insulin-like growth f actor-I (IGF-I) rise during puberty. Previous studies manipulating tes tosterone levels in rats with normal GH secretion suggested that the p ubertal IGF-I rise is regulated by an interaction between GH and sex s teroids. Therefore, in a reciprocal study, IGF-I levels were examined during sexual maturation of the GH-deficient dwarf (dw/dw) rat which h as a selective genetic deficiency of GH but normal sex steroid levels. Male dw/dw rats were treated with daily injections of recombinant hum an GH (200 mu g/100 g body weight) or saline vehicle, from 28 to 70 da ys of age. Sexual maturation was determined to occur primarily between 42 and 63 days of age based on testis and seminal vesicle growth and plasma testosterone levels. GH treatment had no effect on seminal vesi cle weights, plasma testosterone or gonadotrophins. GH administration resulted in a 7% increase in absolute testes weight (P<0.05), but a 50 % increase in body weight (P<0.0001). These results supported previous findings that the reproductive development of dw/dw rats is essential ly normal. Untreated dw/dw rats had no rise in IGF-I levels during sex ual maturation. In contrast, treatment with GH produced a marked susta ined rise in IGF-I levels (P<0.0001). Ligand blots demonstrated GH ind uction of IGF-binding protein-3 (IGFBP-3) and an IGFBP cluster at 32 k Da. The initially high immunoreactive IGFBP-1 levels (>600 ng/ml) decr eased by 49 days of age after which untreated dw/dw rats had significa ntly higher IGFBP-1 levels than GH-treated dw/dw rats (P<0.01). We con clude that GH secretion, rather than sex steroids, may be the predomin ant determinant of pubertal IGF-I levels in rats and that the rise in circulating IGF-I levels during puberty is not an indispensible event for normal reproductive development.