"Changes in morphology and gene expression of dynorphin neurons in the infundibular nucleus of postmenopausal women¡¨

ABSTRACT
Human menopause is characterized by ovarian failure, gonadotropin hypersecretion and hypertrophy of neurons expressing neurokinin B (NKB) and kisspeptin mRNA within the hypothalamic infundibular nucleus. In the arcuate (infundibular) nucleus of the rat and ewe, NKB is colocalized with dynorphin, an endogenous opioid peptide. In this study, we determine if there are alterations in the size and number of neurons expressing dynorphin mRNA in the infundibular nucleus of postmenopausal women. In situ hybridization was performed on sagittal hypothalamic sections from premenopausal (n=3) and postmenopausal (n=3) women using a radiolabeled cDNA probe targeted to dynorphin mRNA. Similar to NKB and kisspeptin neurons, dynorphin mRNA-expressing neurons in the postmenopausal infundibular nucleus displayed morphological features of hypertrophy. This impression was confirmed by quantitative analysis. The mean profile area of dynorphin neurons in the infundibular nucleus was increased in postmenopausal women (PRE: 156.3 ¡Ó 4.5 £gm2; POST: 341.9 ¡Ó 2.1 £gm2, p < 0.001). However, in contrast to the increased number of neurons expressing NKB or kisspeptin mRNAs in the postmenopausal human hypothalamus, the mean number of dynorphin mRNA-expressing neurons was significantly decreased (PRE: 101.67 ¡Ó 6.57 neurons/section; POST: 27 ¡Ó 8.7 neurons/section, p < 0.005). Our studies provide indirect evidence that NKB, kisspeptin and dynorphin are colocalized in the hypertrophied neurons of the infundibular nucleus of postmenopausal women. Given the inhibitory role of dynorphin in reproductive regulation, a decrease in dynorphin gene expression could contribute to the gonadotropin hypersecretion that occurs in postmenopausal women.