EFFECTS OF LONG-TERM GONADOTROPIN-RELEASING-HORMONE ANALOG TREATMENT ON GROWTH, GROWTH-HORMONE (GH) SECRETION, GH RECEPTORS, AND GH-BINDINGPROTEIN IN THE RAT

Long-acting gonadotropin-releasing hormone (GnRH) analogs (GnRH-a) sup press gonadal steroid production and are used in precocious puberty, r esulting in an arrest of pubertal development, a slower epiphyseal mat uration, and a deceleration of growth, but an increased final height. However, the way that GnRH-a affect growth is not clear. GnRH-a treatm ent might not only affect gonadal steroid production but might also mo dulate the GH axis and thereby affect growth. We used a rat model to i nvestigate the long-term effects of prepubertally started GnRH-a treat ment (triptorelin) on growth, spontaneous GH secretion, hepatic GH rec eptors (GHR), and GH-binding protein (GHBP) and compared it with surgi cal gonadectomy. Triptorelin affected most parameters in the same dire ction as surgical gonadectomy but to a lesser extent. In females, grow th was enhanced by triptorelin, baseline GH secretion was decreased, a nd hepatic GHR and GHBP were decreased. Apart from these effects on th e GH axis, reduction of the direct inhibiting effect of estrogen on gr owth could be responsible for the triptorelin-induced growth. In males , triptorelin treatment enhanced body weight gain and slightly enhance d gain in length. GH peak amplitude was the only parameter of GH secre tion affected and decreased, whereas GHR or GHBP were not affected. Th is stimulation of weight gain by long-term triptorelin treatment in ma le rats, which is opposite the effect of surgical gonadectomy, could i ndicate an interference of GnRH-a in the hormonal regulation of food i ntake and body weight control. We conclude that triptorelin treatment affected growth and the GH-GHR-GHBP axis in rats, more markedly in fem ales than in males. However, triptorelin was not as effective as surgi cal gonadectomy.