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Horm Metab Res 2012; 44(06): 451-457
DOI: 10.1055/s-0032-1306309
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Differential Response of the Primate HPG Axis to N-Methyl-d, l-aspartate, but not to Kisspeptin Challenge under Euglycemic and Hypoglycemic Conditions

F. Wahab   *
1    Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
2    Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KPK, Pakistan
,
W-uz. Zaman   *
1    Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
M. Shahab
1    Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
› Author Affiliations
Further Information

Publication History

received 24 November 2011

accepted 14 February 2012

Publication Date:
02 April 2012 (online)

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Abstract

Hypoglycemia inhibits the hypothalamic-pituitary-gonadal (HPG) axis by still incompletely deciphered mechanisms. Many evidences suggest that the hypoglycemia-induced inhibition of the HPG axis involves alteration of the hypothalamic gonadotropin-releasing hormone (GnRH) release, but neuroendocrine factors responsible for this alteration are yet to be completely elucidated. The current study was carried out to ascertain whether insulin-induced hypoglycemic suppression of the HPG axis involves modulation of responsiveness of the GnRH neuron to kisspeptin and excitatory amino acids (EAA) drives. Five intact chair-restraint habituated adult male rhesus monkeys (Macaca mulatta) were given intravenous boli of GnRH, hCG, human kisspeptin-10 (KP10), NMDA (N-methyl-d, l-aspartate, an EAA analogue), and vehicle in both insulin (1 IU/kg)-induced hypoglycemic (IIH) and normal euglycemic conditions. Specific RIAs were used for measuring plasma cortisol and T concentrations. KP10 and NMDA administration stimulated significantly (p<0.005) T secretion in both euglycemic and hypoglycemic monkeys. Mean post-KP10 T concentrations and AUC were comparable between euglycemic and hypoglycemic monkeys. However, mean post-NMDA T levels and AUC in hypoglycemic animals were significantly lower (p<0.01–0.005) as compared to the corresponding values in euglycemic animals. T response to GnRH and hCG was similar between hypoglycemic and euglycemic monkeys. Vehicle did not affect plasma T concentrations in all conditions. Our results demonstrate that while the primate HPG axis response to kisspeptin stimulation remains intact that to EAA excitation is attenuated in hypoglycemic conditions, suggesting that hypogonadism in IIH is contributed, in part, by reduced sensitivity of the GnRH neurons to EAA signaling in the primate hypothalamus.

Key words

hypoglycemia - kisspeptin - GPR54 - NMDA - EAA - GnRH - testosterone
* 

* These authors contributed equally to this work.


 

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