Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta).
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wahab
Fazal
F
Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Aziz
Farzana
F
Irfan
Shahzad
S
Zaman
Waheed-Uz
WU
Shahab
Muhammad
M
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005215:Fasting / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology*; D007649:Ketamine / Q000494:pharmacology; D059648:Kisspeptins; D008253:Macaca mulatta; D008297:Male; D011863:Radioimmunoassay; D013739:Testosterone / Q000097:blood; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
D001786:Blood Glucose; D006063:Chorionic Gonadotropin; D018691:Excitatory Amino Acid Antagonists; C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D013739:Testosterone; D007649:Ketamine; D006854:Hydrocortisone