Niepsuj, T.;Nurani, R.;Oliveira, G.;Johnson, A.;Nguyen, A.;Ebert, K.;Farhat, W.;Jorgensen, J.;Auger, A.

Purpose Puberty is regulated by activation of the hypothalamic-pituitary-gonadal (HPG) axis, which drives reproductive maturation. Gonadotropin releasing hormone (GnRH) agonists are clinically used to delay pubertal progression by suppressing this axis. While GnRH agonists have long been used clinically to delay pubertal progression, the developmental characterization of sustained HPG axis suppression during this critical period remains incompletely understood. Thus, We examined the effects of GnRH receptor agonism in juvenile rats. Hypothesis Sustained GnRH receptor agonism will: (1) result in lower gonadal mass and size, (2) delay or blunt peripheral pubertal landmarks, and (3) alter hormonal signaling dynamics within the HPG axis. Methods Male and female Sprague-Dawley rats (48) were injected with a single dose of extended release leuprolide acetate depot (LA) or vehicle control (n=12/group) on postnatal day (PND) 23. On PND 44, animals were euthanized and then assessed for changes in mass, markers of peripheral puberty, pituitary gene expression, and hormone concentrations in serum and gonads. Results In females, LA treatment resulted in lower gonad size, increased body mass, and blunted peripheral signs of puberty. In males, LA treatment resulted in lower gonad size but did not alter body mass, with less pronounced effects on peripheral puberty. In the pituitary, LA treated rats had lower levels of gonadotropin signaling transcripts ( Gnrhr , Fshb , & Lhb mRNA ) regardless of sex, but higher Cga and Nr5a1 mRNA levels in females. Serum FSH and ACTH levels were lower in LA treated animals regardless of sex, while treated females had lower progestins and increased LH levels. No changes were observed in intragonadal steroids. Conclusions LA treatment reduced aspects of pubertal maturation and HPG axis output, with sex specific outcomes. These findings highlight the need for integrated, multi-level approaches to understand how altered GnRH signaling impacts pubertal and long-term physiology.