Increased testicular insulin-like growth factor 1 is associated with gonadal activation by recombinant growth hormone in immature rats

Abstract

Background In children, recombinant human growth hormone (rhGH) therapy for treatment of short stature has raised concerns of the early onset of puberty. Puberty is initiated by the activation of the hypothalamus-pituitary-gonad axis. Insulin-like growth factor-1 (IGF1) has been known to mediate physiologic effects of GH. To understand the mechanism of precocious sexual maturation following prepubertal GH therapy, the effects of rhGH on the hypothalamus-pituitary-gonad axis were examined in the immature male rats. Methods Immature male rats were given by daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30. The effects of rhGH on kisspeptin-GnRH-LH system in the hypothalamus-pituitary axis, systemic and testicular IGF1, spermatogenesis, steroidogenesis, and circulating testosterone levels were examined. The effects of rhGH on the IGF1 expression and steroidogenesis were examined in progenitor LCs in vitro. Results Testicular steroidogenic pathway and spermatogenesis marker mRNA levels, number and size of 17β-hydroxysteroid dehydrogenase (+) LCs, and blood testosterone levels of rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA of rhGH rats were significantly higher than those of controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels of rhGH rats were significantly higher than those of controls on PND 24 but significantly lower than those of controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas circulating IGF1 levels were not. In progenitor LCs, rhGH significantly increased Igf1 and steroidogenic pathway mRNA levels and testosterone production. Conclusions Local increases in testicular IGF1 might be an important mediator of gonadal maturation via activation of LCs steroidogenesis in immature rats given rhGH.

Dysregulation of testis mRNA expression levels in hatchery-produced vs wild greater amberjack Seriola dumerili

“…The pathway “cell cycle” includes genes involved in cell proliferation. The pathways “progesterone-mediated oocyte maturation” and “oocyte meiosis”, despite the names they have been assigned, include genes related to both oogenesis and spermatogenesis processes; e.g., spyda encodes for a cell cycle regulator that plays a role in male germ cell meiotic maturation 43 ; igf 1 is associated with testicular activation by recombinant growth hormone in rats 44 and with testicular germ cell proliferation and apoptosis in fish 45 ; aurka is required for male germline maintenance and regulates sperm motility in mice 46 .…”

Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis

“…In the testes, IGF1 and its receptor (IGFR) are present in Sertoli, Leydig, germ, and peritubular cells [119,130,135,136]. In rodent Leydig cells, IGF1 secretion and upregulation of IGFR can be stimulated by LH, hCG, and GH [137][138][139][140].…”