Pubertal Triptorelin Exposure Alters Hypothalamic Reproductive–Metabolic Integration in a Sex-Specific Manner
Simple Summary Reproduction is primarily regulated by the hypothalamic–pituitary–gonadal axis: gonadotropin-releasing hormone (GnRH), produced by neurons in the hypothalamus, acts on the pituitary gland that produces hormones controlling gonadal (ovarian and testicular) functions. Puberty is the process of reproductive maturation that involves the activation of GnRH neurons and the pulsatile release of GnRH. GnRH agonists (GnRHa) are synthetic molecules similar to GnRH that are used as puberty blockers to treat premature puberty and as a part of treatment in some transgender adolescents. We used GnRHa to treat male and female rats at the start of puberty and examined its effects on reproductive functions and metabolism. GnRHa treatment induced the suppression of reproductive function in rats of both sexes, evidenced by changes in ovaries and testes and in pituitary markers important for the control of reproduction. The effects on metabolism were sex-specific: treated females gained more weight and had a higher food intake than controls, while treated males exhibited decreased weight gain and changes in locomotion compared to controls. Also, only females showed changes in the hypothalamic molecules regulating the energy balance. These results demonstrate that puberty blockers exert broader impact than suppressing reproductive maturation and highlight the importance of further research of their effects.