Stereologic study of the hypothalamic infundibular nucleus in young and older women

Abstract

Aging in women is associated with dramatic changes in neuronal morphology and neuropeptide gene expression in the medial basal hypothalamus. There is hypertrophy of neurons expressing substance P and neurokinin B gene transcripts in the infundibular (arcuate) nucleus, accompanied by increased tachykinin gene expression. In addition, gonadotropin-releasing hormone (GnRH) gene expression is increased in a separate subpopulation of neurons within the medial basal hypothalamus. In contrast, the number of neurons expressing proopiomelanocortin (POMC) mRNA in the infundibular nucleus of older women is decreased. To determine whether neuronal degeneration contributes to these phenomena, unbiased stereologic methods were used to compare the total number of infundibular neurons between groups of young (premenopausal) and older (postmenopausal) women. There was no significant difference in the total number of infundibular neurons between young (520,000 +/- 42,000 neurons, mean +/- SEM) and older women (505,000 +/- 51,000 neurons, mean +/- SEM). The mean volume of neuronal somata, however, was increased by 40% in the older women (young, 1,860 +/- 180 microm(3) vs. older, 2,610 +/- 230 microm(3), mean +/- SEM, P < 0.05). These data demonstrate that neuronal hypertrophy in older women is not accompanied by degeneration of the infundibular nucleus. We conclude that the loss of menstrual cyclicity in middle-aged women cannot be explained by loss of neurons within the hypothalamic control center for reproduction.

Hypertrophy and Increased Kisspeptin Gene Expression in the Hypothalamic Infundibular Nucleus of Postmenopausal Women and Ovariectomized Monkeys

“…1). As previously described (1,2,4), numerous neurons in the infundibular nucleus of postmenopausal women displayed morphological features of hypertrophy (Fig. 2), and most of these hypertrophied neurons were labeled with the KiSS-1 probe.…”

“…A pronounced enlargement of neurons occurs in the hypothalamic infundibular (arcuate) nucleus of postmenopausal women (1)(2)(3)(4). This cellular hypertrophy is characterized by increased Nissl substance (indicative of increased protein synthesis) and enlarged nuclei and nucleoli, suggesting increased neuronal activity (3,4).…”

“…This cellular hypertrophy is characterized by increased Nissl substance (indicative of increased protein synthesis) and enlarged nuclei and nucleoli, suggesting increased neuronal activity (3,4). The neuronal hypertrophy does not appear to be a compensatory response to cell degeneration because there is neither cell loss nor signs of a pathological process in the infundibular nucleus of older women (2,4). Hybridization histochemistry studies have shown that the hypertrophied neurons express estrogen receptor ␣ (ER␣) and neurokinin B (NKB) mRNA and that menopause is associated with a striking increase in NKB gene expression (2,3).…”

Secrets of the lac Operon

“…In a series of studies we have found that hypothalamic ␣-melanocyte-stimulating hormone, which is produced from the proopiomelanocortin (POMC) precursor and is preferentially reduced during aging [68][69][70][71][72][73], is reduced by fasting and in genetic obesity [74], and is reduced by gold thioglucose [75]. POMC neurons are stimulated by glucose and other nutritional factors [76], and transgenic correction of reduced hypothalamic POMC corrects impairments in glucose homeostasis in obese mice [77].…”

Changes in Estrogen Receptor-α and -β in the Infundibular Nucleus of the Human Hypothalamus Are Related to the Occurrence of Alzheimer’s Disease Neuropathology

“…Hypertrophy and hyperactivity in the infundibular nucleus of postmenopausal women are found in neurons expressing estrogen receptors (ERs), neurokinin B (NKB), or substance P (SP) gene transcripts (8,9). Hypertrophy of neurons in this nucleus is thus not a compensation for a loss of neurons but rather the result of activation due to the loss of the estrogen feedback in menopause (8,10). In addition, some hypertrophy, although to a much lesser degree, also occurs in elderly men (11).…”