Age-Related Differences in the Release of Luteinizing Hormone and Gonadotropin-Releasing Hormone in Ovariectomized Rats

Hwang, Chensol; Pu, Hsiao Fung; Hwang, Chih Yang; Liu, Jer Yuh; Yao, Hung Chang; Tung, Yuh Fan; Wang, Paulus S.

doi:10.1159/000125562

Cited by 35 publications

(19 citation statements)

References 21 publications

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“…The second possibility was suggested earlier [26, 27, 28, 29, 30], and the present results support it, but the first one was also quite probable. There have been several demonstrations that aging decreases the transmitter release in response to K + depolarization or electrical stimulation in the CNS neurons.…”

Section: Discussionsupporting

confidence: 88%

Electrical Activity of the Pulse Generator of Gonadotropin-Releasing Hormone in 26-Month-Old Female Rats

Sano

Kimura²

2000

Neuroendocrinology

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To know whether age-related changes occur in the activity of the pulse generator of gonadotropin-releasing hormone (GnRH), old (26 months) and young (3 months) female rats were examined by recording multiunit activity (MUA) in the median eminence region of the hypothalamus, concurrently with blood samplings through an intra-atrial cannula at 6-min intervals to determine serum luteinizing hormone (LH) concentrations. We have regarded the MUA showing intermittent increases (volleys) at 20–30 min intervals, followed by LH pulses, as the electrical activity of the GnRH pulse generator. We were successful in recording MUA in 18 (26%) of 69 old ovariectomized rats and in 8 (32%) of 25 young ovariectomized rats. The overall mean (±SE) of the interval between MUA volleys in old ovariectomized rats was 35.1 ± 2.0 min (n = 18), which was significantly longer than that of 22.5 ± 1.5 min (n = 8) in young ovariectomized rats. The mean interval between LH pulses in old ovariectomized rats was 32.2 ± 3.6 (n = 10), also being significantly longer than that of 23.3 ± 1.0 (n = 8) in young ovariectomized rats. Further, the LH pulse amplitude in old rats (0.95 ± 0.07 ng/ml) was significantly smaller than in young rats (3.40 ± 0.36 ng/ml). The present study also confirmed that the increase in serum LH after intravenous injection of 50 ng GnRH was much smaller in old ovariectomized rats. These results show that the electrical activity of the GnRH pulse generator is certainly reduced with age. Taken together with findings suggesting an age-dependent decrease in stimulated transmitter release, attenuation in both frequency and amplitude of GnRH pulses as well as in pituitary responsiveness to GnRH pulses may account for the decreased pulsatile LH secretion observed in aging rats.

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Section: Discussionsupporting

confidence: 88%

Electrical Activity of the Pulse Generator of Gonadotropin-Releasing Hormone in 26-Month-Old Female Rats

Sano

Kimura²

2000

Neuroendocrinology

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“…In intact (proestrous), OVX, or OVX plus estradiol-treated female rats (the latter during the LH surge), Rubin (1992) reported that basal GnRH release is higher from isolated hypothalami of middle-aged than young rats, although potassium-stimulated GnRH release is equivalent between the two ages. A different result was reported by Hwang et al (1990), who demonstrated that basal GnRH release from explants of young (, 4 months) and old (21 -24 months) OVX rats is comparable, whereas potassium-stimulated GnRH release is greater in the young rats. Differences between these two reports may be due to differences in ages of animals, as the Hwang study used much older rats than the Rubin study.…”

Section: In Vitro Release Of Gnrhcontrasting

confidence: 56%

Neuroendocrine control of reproductive aging: roles of GnRH neurons

Yin

Gore²

2006

Reproduction

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The process of reproductive senescence in many female mammals, including humans, is characterized by a gradual transition from regular reproductive cycles to irregular cycles to eventual acyclicity, and ultimately a loss of fertility. In the present review, the role of the hypothalamic gonadotropin-releasing hormone (GnRH) neurons is considered in this context. GnRH neurons provide the primary driving force upon the other levels of the reproductive axis. With respect to aging, GnRH cells undergo changes in biosynthesis, processing and release of the GnRH decapeptide. GnRH neurons also exhibit morphologic and ultrastructural alterations that appear to underlie these biosynthetic properties. Thus, functional and morphologic changes in the GnRH neurosecretory system may play causal roles in the transition to acyclicity. In addition, GnRH neurons are regulated by numerous inputs from neurotransmitters, neuromodulators and glia. The relationship among GnRH cells and their inputs at the cell body (thereby affecting GnRH biosynthesis) and the neuroterminal (thereby affecting GnRH neurosecretion) is crucial to the function of the GnRH system, with age-related changes in these relationships contributing to the reproductive senescent process. Therefore, the aging hypothalamus is characterized by changes intrinsic to the GnRH cell, as well as its regulatory inputs, which summate to contribute to a loss of reproductive competence in aging females. Reproduction (2006) 131 403-414

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“…It has been well documented for the reproductive axis that the hypothalamus of aged animals has a blunted response to estrogen deprivation or replacement compared with young animals (45)(46)(47)(48)(49)(50)(51)(52). This may be caused, at least in part, by the condition of constant estrous or diestrous, because both conditions involve constant levels of unopposed estrogen rather than the normal fluctuations of estradiol and progesterone in the ovarian cycle (53)(54)(55), and this condition in the aged animal may underlie the blunted spine response we observed.…”

Section: Discussionmentioning

confidence: 99%

Different modes of hippocampal plasticity in response to estrogen in young and aged female rats

Adams

Shah

Janssen

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

207

155

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Estrogen regulates hippocampal dendritic spine density and synapse number in an N-methyl-D-aspartate (NMDA) receptor-dependent manner, and these effects may be of particular importance in the context of age-related changes in endocrine status. We investigated estrogen's effects on axospinous synapse density and the synaptic distribution of the NMDA receptor subunit, NR1, within the context of aging. Although estrogen induced an increase in axospinous synapse density in young animals, it did not alter the synaptic representation of NR1, in that the amount of NR1 per synapse was equivalent across groups. Estrogen replacement in aged female rats failed to increase axospinous synapse density; however, estrogen up-regulated synaptic NR1 compared with aged animals with no estrogen. Therefore, the young and aged hippocampi react differently to estrogen replacement, with the aged animals unable to mount a plasticity response generating additional synapses, yet responsive to estrogen with respect to additional NMDA receptor content per synapse. These findings have important implications for estrogen replacement therapy in the context of aging.A t the turn of the century, the life expectancy of American women was roughly equivalent to the average age of the onset of menopause (1). Presently, there is a 30-year discrepancy between these two demographic indices, with a life expectancy of Ϸ80 years and the average onset of menopause remaining in the early fifties (1). As such, it is critical that we understand the interaction of reproductive senescence with the aging of other systems, particularly the nervous system. The regulation of the reproductive axis by estrogens has been characterized in great detail (2). However, estrogens also impact synaptic communication in brain regions involved in cognitive processing, such as the hippocampus (3), and these effects may be of particular importance in the context of aging when both circulating estrogen levels change and hippocampal-dependent functions decline. With respect to its nonreproductive functions, estrogen improves verbal memory and the capacity for learning new associations in both naturally and surgically menopausal women (4). In rats, although findings are somewhat controversial (5-7), learning was enhanced during the proestrus phase (i.e., high estrogen) of the estrous cycle compared with the estrus phrase (i.e., low estrogen) (8). Another study found improved learning and memory on the Morris water maze task in ovariectomized animals with intrahippocampal estrogen injection compared with saline injection (9).Our current understanding of estrogen effects on synaptic plasticity in the hippocampus is based almost exclusively on data from young animals. For example, dendritic spine density in CA1 pyramidal cells is sensitive to naturally occurring estrogen fluctuations in young animals (10), as well as experimentally induced estrogen depletion and replacement (11)(12)(13)(14). Recent evidence suggests that estrogens mediate these morphological changes through N-methyl-D-...

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Age-Related Differences in the Release of Luteinizing Hormone and Gonadotropin-Releasing Hormone in Ovariectomized Rats

Cited by 35 publications

References 21 publications

Electrical Activity of the Pulse Generator of Gonadotropin-Releasing Hormone in 26-Month-Old Female Rats

Electrical Activity of the Pulse Generator of Gonadotropin-Releasing Hormone in 26-Month-Old Female Rats

Neuroendocrine control of reproductive aging: roles of GnRH neurons

Different modes of hippocampal plasticity in response to estrogen in young and aged female rats

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