Archive | 2021
Increased Testicular Insulin-like Growth Factor 1 is Associated with Gonadal Activation by Recombinant Growth Hormone in Immature Rats
Abstract
\n To understand the mechanism of precocious sexual maturation following prepubertal growth hormone (GH) therapy, the effects of recombinant human GH (rhGH) on the kisspeptin-gonadotropin-releasing hormone-luteinizing hormone (GnRH-LH) system in the hypothalamus-pituitary axis, systemic and testicular insulin-like growth factor-1 (IGF1), spermatogenesis and Leydig cell steroidogenesis, and circulating testosterone levels were examined in immature rats. Following daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30, testicular steroidogenic pathway genes and spermatogenesis marker genes mRNA levels, the number and size of HSD17B(+) Leydig cells, and blood testosterone levels in the rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA in the rhGH rats were significantly higher than those in the controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels in rhGH rats were significantly higher than those in the controls on PND 24 but significantly lower than those in controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas liver Igf1 mRNA levels and circulating IGF1 levels were not. In progenitor Leydig cells, rhGH significantly increased the Igf1 and steroidogenic pathway genes mRNA levels and the testosterone production. Therefore, local increases in testicular IGF1 might be an important mediator of gonadal activation via steroidogenic activation of Leydig cells in immature rats given rhGH.