Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism by neonatal testosterone

The influence of endogenous sex steroids and exogenous testosterone treatment on pulsatile GH secretion, body weight, longitudinal bone growth, and hepatic steroid metabolism was studied in male and female adult rats. Blood samples were obtained from the tip of the tail, and maximum and minimum GH levels were determined in individual rats to evaluate pulse heights and baseline levels. Longitudinal bone growth was measured using the intravital marker tetracycline, and hepatic steroid metabolism was evaluated by determining the enzyme activities of 16α-hydroxylase and 5α-reductase. Neonatal, but not prepubertal, gonadectomy of male rats suppressed maximum and mean plasma GH levels during adult life. The body weight and the rate of longitudinal bone growth were also decreased. Testosterone treatment neonatally reversed all of these effects. Neonatal gonadectomy of male rats also caused an elevation of minimum plasma GH levels, an effect, however, which was not reversed by testosterone replacement during neonatal life. Neonatally gonadectomized females treated with testosterone neonatally or during adult life increased their maximum and decreased their minimum GH levels. Their longitudinal bone growth was increased. The body weight of these rats was increased by neonatal, but not adult, testosterone treatment. There was no effect of neonatal ovariectomy on plasma GH levels in 3- to 4-month-old female rats. However, neonatal ovariectomy did increase the maximum and mean plasma GH levels immediately postpubertally, suggesting that the effect of the ovaries on GH secretion differs among mature female rats of different ages. Prepubertal gonadectomy of male rats feminized their hepatic steroid metabolism by decreasing 16α-hydroxylase and increasing 5α-reductase activities. Neonatal gonadectomy caused an even more pronounced feminization, which was partly reversed in rats given testosterone replacement therapy neonatally. In neonatally gonadectomized female rats, treatment with testosterone during adult life increased 16α-hydroxylase and decreased 5α-reductase to levels seen in intact male rats. The present results indicate that neonatally secreted testicular androgens imprint the high amplitude pulses characteristic of GH secretion in adult male rats. Neonatal adrogens also stimulate somatic growth and partially account for the masculinized hepatic steroid metabolism in the adult animal. It is proposed that imprinting of the GH secretory pattern contributes to the influence of neonatal testicular androgens on body growth and hepatic steroid-metabolizing enzymes.