Menopause and the human hypothalamus: Evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback

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Abstract

Menopause is characterized by depletion of ovarian follicles, a reduction of ovarian hormones to castrate levels and elevated levels of serum gonadotropins. Rather than degenerating, the reproductive neuroendocrine axis in postmenopausal women is intact and responds robustly to the removal of ovarian hormones. Studies in both human and non-human primates provide evidence that the gonadotropin hypersecretion in postmenopausal women is secondary to increased gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. In addition, menopause is accompanied by hypertrophy of neurons in the infundibular (arcuate) nucleus expressing KiSS-1, neurokinin B (NKB), substance P, dynorphin and estrogen receptor α (ERα) mRNA. Ovariectomy in experimental animals induces nearly identical findings, providing evidence that these changes are a compensatory response to ovarian failure. The anatomical site of the hypertrophied neurons, as well as the extensive data implicating kisspeptin, NKB and dynorphin in the regulation of GnRH secretion, provide compelling evidence that these neurons are part of the neural network responsible for the increased levels of serum gonadotropins in postmenopausal women. We propose that neurons expressing KiSS-1, NKB, substance P, dynorphin and ERα mRNA in the infundibular nucleus play an important role in sex-steroid feedback on gonadotropin secretion in the human.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalPeptides
Volume30
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Neurokinin B
Kisspeptins
Menopause
Gonadotropins
Arcuate Nucleus of Hypothalamus
Hypothalamus
Neurons
Estrogens
Feedback
Neurokinin-1 Receptors
Gonadotropin-Releasing Hormone
Estrogen Receptors
Hormones
Dynorphins
Messenger RNA
Ovarian Follicle
Ovariectomy
Serum
Hypertrophy
Primates

Keywords

  • Aging
  • Estrogen
  • GnRH
  • Ovary
  • Pituitary
  • Progesterone
  • Reproduction
  • Steroid feedback

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "Menopause is characterized by depletion of ovarian follicles, a reduction of ovarian hormones to castrate levels and elevated levels of serum gonadotropins. Rather than degenerating, the reproductive neuroendocrine axis in postmenopausal women is intact and responds robustly to the removal of ovarian hormones. Studies in both human and non-human primates provide evidence that the gonadotropin hypersecretion in postmenopausal women is secondary to increased gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. In addition, menopause is accompanied by hypertrophy of neurons in the infundibular (arcuate) nucleus expressing KiSS-1, neurokinin B (NKB), substance P, dynorphin and estrogen receptor α (ERα) mRNA. Ovariectomy in experimental animals induces nearly identical findings, providing evidence that these changes are a compensatory response to ovarian failure. The anatomical site of the hypertrophied neurons, as well as the extensive data implicating kisspeptin, NKB and dynorphin in the regulation of GnRH secretion, provide compelling evidence that these neurons are part of the neural network responsible for the increased levels of serum gonadotropins in postmenopausal women. We propose that neurons expressing KiSS-1, NKB, substance P, dynorphin and ERα mRNA in the infundibular nucleus play an important role in sex-steroid feedback on gonadotropin secretion in the human.",
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