Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset.
Semaan. Sheila J SJ; Kauffman. Alexander S AS
Key Findings
- Male mice show increasing Kiss1 and Tac2 in the hypothalamus during puberty, but levels stay lower than in females
- Rfrp expression drops in both sexes during the same period
- No sex differences were seen in KNDy neuron activation or Kiss1r expression in GnRH neurons
Practical Outcomes
- For biohackers, the findings are mainly of academic interest and don’t translate into actionable dosing or interventions. It suggests that manipulating kisspeptin pathways could someday affect puberty timing, but no safe or effective protocols exist for humans yet.
Summary
This mouse study shows that the brain chemicals kisspeptin (Kiss1) and neurokinin B (Tac2) rise during puberty in boys, but not as much as in girls, while another peptide, RFRP, drops similarly in both sexes. The differences in these hormone signals might help explain why girls start puberty earlier than boys, but the work is basic science and doesn’t give direct advice for human health or anti‑aging protocols.
Abstract
The mechanisms regulating puberty still remain elusive, as do the underlying causes for sex differences in puberty onset (girls before boys) and pubertal disorders. Neuroendocrine puberty onset is signified by increased pulsatile GnRH secretion, yet how and when various upstream reproductive neural circuits change developmentally to govern this process is poorly understood. We previously reported day-by-day peri-pubertal increases (Kiss1, Tac2) or decreases (Rfrp) in hypothalamic gene expression of female mice, with several brain mRNA changes preceding external pubertal markers. However, similar pubertal measures in males were not previously reported. Here, to identify possible neural sex differences underlying sex differences in puberty onset, we analyzed peri-pubertal males and directly compared them with female littermates. Kiss1 expression in male mice increased over the peri-pubertal period in both the AVPV and ARC nuclei but with lower levels than in females at several ages. Likewise, Tac2 expression in the male ARC increased between juvenile and older peri-pubertal stages but with levels lower than females at most ages. By contrast, both DMN Rfrp expressionand Rfrp neuronal activation strongly decreased in males between juvenile and peri-pubertal stages, but with similar levels as females. Neither ARC KNDy neuronal activation nor Kiss1r expression in GnRH neurons differed between males and females or changed with age. These findings delineate several peri-pubertal changes in neural populations in developing males, with notable sex differences in kisspeptin and NKB neuron developmental patterns. Whether these peri-pubertal hypothalamic sex differences underlie sex differences in puberty onset deserves future investigation.
Study Information
pubmed
2022
2022-04-22T00:00:00.000Z
10.1016/j.mce.2022.111654
7
102