PMID- 19094085 OWN - NLM STAT- MEDLINE DCOM- 20090203 LR - 20211020 IS - 1365-2826 (Electronic) IS - 0953-8194 (Print) IS - 0953-8194 (Linking) VI - 20 IP - 12 DP - 2008 Dec TI - Changes in prodynorphin gene expression and neuronal morphology in the hypothalamus of postmenopausal women. PG - 1376-81 LID - 10.1111/j.1365-2826.2008.01796.x [doi] AB - Human menopause is characterised by ovarian failure, gonadotrophin hypersecretion and hypertrophy of neurones expressing neurokinin B (NKB), kisspeptin (KiSS)-1 and oestrogen receptor (ER) alpha gene transcripts within the hypothalamic infundibular (arcuate) nucleus. In the arcuate nucleus of experimental animals, dynorphin, an opioid peptide, is colocalised with NKB, kisspeptin, ER alpha and progesterone receptors. Moreover, ovariectomy decreases the expression of prodynorphin gene transcripts in the arcuate nucleus of the ewe. Therefore, we hypothesised that the hypertrophied neurones in the infundibular nucleus of postmenopausal women would express prodynorphin mRNA and that menopause would be accompanied by changes in prodynorphin gene transcripts. In the present study, in situ hybridisation was performed on hypothalamic sections from premenopausal and postmenopausal women using a radiolabelled cDNA probe targeted to prodynorphin mRNA. Autoradiography and computer-assisted microscopy were used to map and count labelled neurones, measure neurone size and compare prodynorphin gene expression between premenopausal and postmenopausal groups. Neurones expressing dynorphin mRNA in the infundibular nucleus of the postmenopausal women were larger and exhibited hypertrophied morphological features. Moreover, there were fewer neurones labelled with the prodynorphin probe in the infundibular nucleus of the postmenopausal group compared to the premenopausal group. The number of dynorphin mRNA-expressing neurones was also reduced in the medial preoptic/anterior hypothalamic area of postmenopausal women without changes in cell size. No differences in cell number or size of dynorphin mRNA-expressing neurones were observed in any other hypothalamic region. Previous studies using animal models provide strong evidence that the changes in prodynorphin neuronal size and gene expression in postmenopausal women are secondary to the ovarian failure of menopause. Given the inhibitory effect of dynorphin on the reproductive axis, decreased dynorphin gene expression could play a role in the elevation in luteinising hormone secretion that occurs in postmenopausal women. FAU - Rometo, A M AU - Rometo AM AD - Department of Pathology, University of Arizona College of Medicine, Tucson, AZ 85724, USA. FAU - Rance, N E AU - Rance NE LA - eng GR - T32 AG007434/AG/NIA NIH HHS/United States GR - R56 AG009214-15A1/AG/NIA NIH HHS/United States GR - R56 AG009214/AG/NIA NIH HHS/United States GR - R01 AG009214-13/AG/NIA NIH HHS/United States GR - R01 AG009214/AG/NIA NIH HHS/United States GR - R01 AG-09214/AG/NIA NIH HHS/United States GR - R01 AG009214-14/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (Enkephalins) RN - 0 (Protein Precursors) RN - 93443-35-7 (preproenkephalin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Animals MH - Autoradiography MH - Cell Shape MH - Enkephalins/*genetics/metabolism MH - Female MH - *Gene Expression MH - Humans MH - Hypothalamus/*cytology/metabolism MH - Middle Aged MH - *Neurons/cytology/physiology MH - Postmenopause/*physiology MH - Protein Precursors/*genetics/metabolism MH - Young Adult PMC - PMC2893873 MID - NIHMS211657 EDAT- 2008/12/20 09:00 MHDA- 2009/02/04 09:00 PMCR- 2010/06/29 CRDT- 2008/12/20 09:00 PHST- 2008/12/20 09:00 [entrez] PHST- 2008/12/20 09:00 [pubmed] PHST- 2009/02/04 09:00 [medline] PHST- 2010/06/29 00:00 [pmc-release] AID - JNE1796 [pii] AID - 10.1111/j.1365-2826.2008.01796.x [doi] PST - ppublish SO - J Neuroendocrinol. 2008 Dec;20(12):1376-81. doi: 10.1111/j.1365-2826.2008.01796.x.