Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta).
Wahab. Fazal F; Aziz. Farzana F; Irfan. Shahzad S; Zaman. Waheed-Uz WU; Shahab. Muhammad M
Key Findings
- 48‑hour fasting cuts plasma glucose and testosterone and raises cortisol.
- Kisspeptin‑10 still triggers testosterone release, but the total amount and speed of the response are reduced after fasting.
- Direct hCG stimulation of testosterone is not affected by fasting, indicating the effect is upstream at the kisspeptin/GnRH level.
Practical Outcomes
- If you plan to use kisspeptin (or any strategy that relies on the kisspeptin‑GnRH pathway) to boost testosterone, avoid doing so while in a fasted state, as the response will be blunted and delayed. Short fasts may therefore temporarily lower the effectiveness of natural or supplemental kisspeptin for hormone optimization.
Summary
A short 48‑hour fast in adult male rhesus monkeys lowered blood sugar and testosterone and raised cortisol. When the hormone‑mimic kisspeptin‑10 was given, it still boosted testosterone, but the rise was smaller and slower in fasted monkeys. The response to a direct hCG stimulus was unchanged, suggesting the fasting effect is specific to the kisspeptin pathway.
Abstract
In primates, changes in nutritional status affect the hypothalamic-pituitary-gonadal (HPG) axis by still poorly understood mechanisms. Recently, hypothalamic kisspeptin-GPR54 signaling has emerged as a significant regulator of this neuroendocrine axis. The present study was designed to examine whether suppression of the reproductive function by acute food-restriction in a non-human primate is mediated by decreased responsiveness of the HPG axis to endogenous kisspeptin drive. Five intact adult male rhesus monkeys habituated to chair-restraint, received intravenous boli of human kisspeptin-10 (KP10, 50 microg), hCG (50 IU), and vehicle (1 ml) in both fed and 48-h fasting conditions. Plasma concentrations of glucose, cortisol and testosterone (T) were measured by using enzymatic and specific RIAs, respectively. The acute 48-h fasting decreased plasma glucose (P<0.01) and T (P<0.005) levels, and increased cortisol levels (P<0.05). KP10 administration caused a robust stimulation of T secretion in both fed and fasted monkeys. However, mean T concentration and T AUC after KP10 administration were significantly (P<0.01-0.005) reduced in fasted monkeys. Likewise, the time of the first significant increase in post-KP10 T levels was also significantly (P<0.01) delayed. T response to hCG stimulation was similar in fed and fasted monkeys. The present results indicate that under fasting conditions the KP10 induced T response is delayed and suppressed. These data support the notion that fasting-induced suppression of the HPG axis in the adult male rhesus monkey may involve, at least in part, a reduction in the sensitivity of the GnRH neuronal network to endogenous kisspeptin stimulation.
Study Information
pubmed
2008
2008-09-16T00:00:00.000Z
10.1016/j.lfs.2008.09.001
52
42