Dose-Dependent Degeneration of Leydig Cells Following Kisspeptin-10 Administration: An Ultrastructural Study.
Ramzan. Faiqah F; Qureshi. Irfan Zia IZ; Ramzan. Muhammad Haris MH
Key Findings
- Repeated intraperitoneal injections of kisspeptin-10 reduced plasma testosterone in a dose‑dependent manner.
- Electron microscopy showed structural damage to Leydig cells (shrunken nuclei, organelle swelling, vacuoles) after kisspeptin‑10 treatment.
- Higher doses led to greater Leydig cell loss and increased interstitial cell hyperplasia.
Practical Outcomes
- For biohackers considering kisspeptin‑10 to modulate reproductive hormones, the study warns that chronic or high‑dose use may actually lower testosterone and harm testicular cells, at least in rats. Because the work was done in pre‑pubertal rats with injections, the findings are not directly transferable to humans, but they suggest caution and the need for low‑dose, short‑term protocols if experimenting with kisspeptin.
Summary
In young male rats, giving kisspeptin-10 repeatedly lowered blood testosterone and caused damage to the testicular Leydig cells that make the hormone. The harmful effects got worse with higher doses. This suggests that chronic, high‑dose kisspeptin-10 could suppress testosterone production, at least in this animal model.
Abstract
The discovery of kisspeptin signaling as a key regulator of gonadotropin- releasing hormone (GnRH) secretion from the hypothalamus enhanced our understanding of the neuroendocrine regulation of mammalian reproduction. Effects of central and peripheral administration of kisspeptin on plasma gonadotropins, testosterone, and spermatogenesis are studied in detail. The present study was conducted to check the ultrastructure of Leydig cells in prepubertal male rats in response to the administration of a range of kisspeptin doses. We administered a range of kisspeptin-10 doses (1 μg, 1 ηg, and 10 ρg) intraperitoneally to prepubertal male Sprague-Dawley rats (PND 35) twice daily after every 12 hours. Control rats were injected with physiological saline in parallel. At the end of the treatment, plasma concentrations of testosterone were measured by competitive binding radioimmunoassay, and small pieces of rat testicular tissue were processed for electron microscopy to examine the ultrastructure of Leydig cells. Plasma testosterone concentration was reduced significantly at 1ηg (P<0.05) and 1μg (P<0.01) doses as compared to control. Distinct ultrastructural changes categorized as dilatation of cytoplasmic organelles, irregularly shaped nuclei with nuclear membrane invaginations, reduced nuclear sizes, degeneration, and vacuolation were observed in the kisspeptin-10 treated Leydig cells as compared to control. Quantification of the data showed reduced Leydig cell indices and hyperplasia of the interstitial cells. It is concluded that chronic intermittent administration of kisspeptin-10 has a dose-dependent degenerative effect on the plasma testosterone levels and Leydig cells ultrastructure in prepubertal male rats.
Study Information
pubmed
2022
2021-12-12T00:00:00.000Z
10.2174/0929866528666211213090033
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