Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system.
Pinilla. L L; Castellano. J M JM; Romero. M M; Tena-Sempere. M M; Gaytán. F F; Aguilar. E E
Key Findings
- Hypothalamic kisspeptin (KiSS-1) and GnRH gene levels were unchanged in hypertensive rats with delayed puberty.
- Ovarian weight, steroid hormone output, and response to human chorionic gonadotropin were dramatically reduced.
- Expression of key steroid‑making enzymes (P450scc, 3β‑HSD, aromatase) was lowered in the ovaries.
Practical Outcomes
- For biohackers, this suggests that simply adding kisspeptin‑10 is unlikely to overcome ovarian failure or delayed puberty caused by intrinsic ovarian problems. Efforts should instead focus on supporting ovarian health and steroidogenesis rather than targeting the kisspeptin pathway alone.
Summary
In a rat model of high blood pressure, delayed puberty was linked to the ovaries not working properly, not to problems with the kisspeptin (KiSS-1) or GnRH hormone systems. The kisspeptin system looked normal, but the ovaries produced far less hormone and responded poorly to stimulation.
Abstract
Spontaneously hypertensive (SH) rats, extensively used as experimental models of essential human hypertension, display important alterations in the neuroendocrine reproductive axis, which manifest as markedly delayed puberty onset in females but whose basis remains largely unknown. We analyze herein in female SH rats: 1) possible alterations in the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems, 2) the integrity of feedback mechanisms governing the hypothalamic-pituitary-ovarian axis, and 3) the control of ovarian function by gonadotropins. Our data demonstrate that, despite overtly delayed puberty, no significant decrease in hypothalamic KiSS-1, GPR54, or GnRH mRNA levels was detected in this strain. Likewise, in vivo gonadotropin responses to ovariectomy and systemic kisspeptin-10 or GnRH administration, as well as in vitro gonadotropin responses to GnRH, were fully preserved in SH rats. Moreover, circulating LH levels were grossly conserved during prepubertal maturation, whereas FSH levels were even enhanced from d 20 postpartum onwards. In striking contrast, ovarian weight and hormone (progesterone and testosterone) responses to human chorionic gonadotropin (CG) in vitro were profoundly decreased in SH rats, with impaired follicular development and delayed ovulation at puberty. Such reduced hormonal responses to human CG could not be attributed to changes in LH/CG or FSH-receptor mRNA expression but might be linked to blunted P450scc, 3beta-hydroxy steroid dehydrogenase, and aromatase mRNA levels in ovaries from SH rats. In conclusion, our results indicate that the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems is normal in SH rats, whereas ovarian development, steroidogenesis, and responsiveness to gonadotropins are strongly compromised.
Study Information
pubmed
2009
2009-02-19T00:00:00.000Z
10.1210/en.2008-1381
14
73