TY - JOUR
T1 - Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys
AU - Rometo, Adonna M.
AU - Krajewski, Sally J.
AU - Voytko, Mary Lou
AU - Rance, Naomi E.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants AG-09214 and NIA T32 AG007434 (to A.M.R. for predoctoral training program in Neuroscience).
PY - 2007/7
Y1 - 2007/7
N2 - Context: Human menopause is characterized by ovarian failure, gonadotropin hypersecretion, and neuronal hypertrophy in the hypothalamic infundibular (arcuate) nucleus. Recent studies have demonstrated a critical role for kisspeptins in reproductive regulation, but it is not known whether menopause is accompanied by changes in hypothalamic kisspeptin neurons. Objectives: Our objective was to map the location of neurons expressing kisspeptin gene (KiSS-1) transcripts in the human hypothalamus and determine whether menopause is associated with changes in the size and gene expression of kisspeptin neurons. In monkeys, our objective was to evaluate the effects of ovariectomy and hormone replacement on neurons expressing KiSS-1 mRNA in the infundibular nucleus. Subjects: Hypothalamic tissues were collected at autopsy from eight premenopausal and nine postmenopausal women and from 42 young cynomolgus monkeys in various endocrine states. Methods: We used hybridization histochemistry, quantitative autoradiography, and computer-assisted microscopy. Results: Examination of human hypothalamic sections revealed that KiSS-1 neurons were located predominantly in the infundibular nucleus. In the infundibular nucleus of postmenopausal women, there was a significant increase in the size of neurons expressing KiSS-1 mRNA and the number of labeled cells and autoradiographic grains per neuron. Similar to postmenopausal women, ovariectomy induced neuronal hypertrophy and increased KiSS-1 gene expression in the monkey infundibular nucleus. Conversely, in ovariectomized monkeys, estrogen replacement markedly reduced KiSS-1 gene expression. Conclusions: The cynomolgus monkey experiments provide strong evidence that the increase in KiSS-1 neuronal size and gene expression in postmenopausal women is secondary to ovarian failure. These studies suggest that kisspeptin neurons regulate estrogen negative feedback in the human.
AB - Context: Human menopause is characterized by ovarian failure, gonadotropin hypersecretion, and neuronal hypertrophy in the hypothalamic infundibular (arcuate) nucleus. Recent studies have demonstrated a critical role for kisspeptins in reproductive regulation, but it is not known whether menopause is accompanied by changes in hypothalamic kisspeptin neurons. Objectives: Our objective was to map the location of neurons expressing kisspeptin gene (KiSS-1) transcripts in the human hypothalamus and determine whether menopause is associated with changes in the size and gene expression of kisspeptin neurons. In monkeys, our objective was to evaluate the effects of ovariectomy and hormone replacement on neurons expressing KiSS-1 mRNA in the infundibular nucleus. Subjects: Hypothalamic tissues were collected at autopsy from eight premenopausal and nine postmenopausal women and from 42 young cynomolgus monkeys in various endocrine states. Methods: We used hybridization histochemistry, quantitative autoradiography, and computer-assisted microscopy. Results: Examination of human hypothalamic sections revealed that KiSS-1 neurons were located predominantly in the infundibular nucleus. In the infundibular nucleus of postmenopausal women, there was a significant increase in the size of neurons expressing KiSS-1 mRNA and the number of labeled cells and autoradiographic grains per neuron. Similar to postmenopausal women, ovariectomy induced neuronal hypertrophy and increased KiSS-1 gene expression in the monkey infundibular nucleus. Conversely, in ovariectomized monkeys, estrogen replacement markedly reduced KiSS-1 gene expression. Conclusions: The cynomolgus monkey experiments provide strong evidence that the increase in KiSS-1 neuronal size and gene expression in postmenopausal women is secondary to ovarian failure. These studies suggest that kisspeptin neurons regulate estrogen negative feedback in the human.
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U2 - 10.1210/jc.2007-0553
DO - 10.1210/jc.2007-0553
M3 - Article
C2 - 17488799
AN - SCOPUS:34447115135
SN - 0021-972X
VL - 92
SP - 2744
EP - 2750
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -