Down-Regulation of Hypothalamic Kisspeptin and its Receptor, Kiss1r, mRNA Expression is Associated with Stress-Induced Suppression of Luteinising Hormone Secretion in the Female Rat

• Published in: Journal of neuroendocrinology 2009-01, Vol.21 (1), p.20-29
• Main Authors: Kinsey-Jones, J. S., Li, X. F., Knox, A. M. I., Wilkinson, E. S., Zhu, X. L., Chaudhary, A. A., Milligan, S. R., Lightman, S. L., O'Byrne, K. T.
• Format: Article
• Language: English
• Subjects: Animals; corticosterone; Corticosterone - pharmacology; Corticotropin-Releasing Hormone - pharmacology; CRF; Down-Regulation; Estradiol - administration & dosage; Female; GPR54; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - metabolism; Kiss1; kisspeptin; Kisspeptins; Luteinizing Hormone - secretion; Ovariectomy; Proteins - genetics; Proteins - metabolism; rat; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Kisspeptin-1; Restraint, Physical; stress; Stress, Psychological; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2008.01807.x

Identification of kisspeptin (Kiss1) and its G protein‐coupled receptor 54 (Kiss1r) as an essential component of the hypothalamic‐pituitary‐gonadal (HPG) axis controlling gonadotrophin secretion raises the possibility that kisspeptin‐Kiss1r signalling may play a critical role in the transduction of stress‐induced suppression of reproduction. We examined the effects of: (i) three different stressors, known to suppress pulsatile luteinising hormone (LH) secretion; (ii) corticotrophin‐releasing factor (CRF); and (iii) corticosterone on Kiss1 and Kiss1r expression in key hypothalamic sites regulating gonadotrophin secretion: the medial preoptic area (mPOA) and arcuate nucleus (ARC). Ovariectomised oestrogen‐replaced rats were implanted with i.v., subcutaneous or i.c.v. cannulae. Blood samples were collected at 5‐min intervals for 5–6 h for detection of LH. Quantitative reverse transcriptase‐polymerase chain reaction was used to determine Kiss1 and Kiss1r mRNA levels in brain punches of the mPOA and ARC collected 6 h after restraint, insulin‐induced hypoglycaemia or lipopolysaccharide stress, or after i.c.v. administration of CRF, or acute or chronic subcutaneous administration of corticosterone. We observed down‐regulation of at least one component of the kisspeptin‐Kiss1r signalling system by each of the stress paradigms within the mPOA and ARC. CRF decreased Kiss1 and Kiss1r expression in both the mPOA and ARC. Both acute and chronic stress levels of corticosterone resulted in a concomitant decrease in Kiss1 and an increase in kiss1r mRNA expression in the mPOA and ARC. This differential regulation of Kiss1 and Kiss1r might account for the lack of effect corticosterone has on pulsatile LH secretion. Considering the pivotal role for kisspeptin‐Kiss1r signalling in the control of the HPG axis, these results suggest that the reduced Kiss1‐Kiss1r expression may be a contributing factor in stress‐related suppression of LH secretion.