Opioid Inhibition of Luteinizing Hormone Release Declines with Age and Acyclicity in Female Rats*

Field, Elizabeth A.; Kuhn, Cynthia M.

doi:10.1210/endo-123-6-2626

Cited by 16 publications

(5 citation statements)

References 47 publications

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“…That is, although the shortest interval produced by naloxone was about 6 min in both rats, the period of the effect was shorter in old ovariectomized rats, as seen in figure 5. This may mean that in these extremely old rats a certain number of opioid neurons and/or opioid receptors are still involved in the tonic inhibition of the activity of the GnRH pulse generator, but they are significantly fewer than those in young rats, as suggested previously [25, 28, 40]. In support of this, the decrease in POMC mRNA levels in the hypothalamus has been reported in old-aged mice [41]and rats [42].…”

Section: Discussionsupporting

confidence: 58%

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: 58%

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

Sano

Kimura²

2000

Neuroendocrinology

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“…A recent report has suggested age-related de clines in the content of opiate receptors in some brain areas [30], Further, age-related declines in opioid inhibition of LH have been reported in intact rats of both sexes [31,32[. In female rats [31], the LH increase after naloxone treatment in 4-to 6-month-old rats was significantly reduced compared with that in 1.5-to 3-month-old rats, and no LH response was ob served in 8-to 11-month-old rats, which results were inter preted as suggestive of age-related declines in opioid neuronal activity or receptor numbers. Considering the age at which our rats were OVX in the present study, 32-week OVX rats were 10 months old, so that it is plausible that such a hypothesis is ap plicable to the results of the present study.…”

Section: Discussionmentioning

confidence: 97%

Naloxone Affects the Luteinizing Hormone Secretory Pattern in the Short- and Long-Term Ovariectomized Rat

Funabashi

Kato

Kimura³

1990

Neuroendocrinology

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The effect of naloxone, an opiate receptor antagonist, on the secretory pattern of luteinizing hormone (LH) was evaluated in 4-, 16- and 32-week ovariectomized (OVX) rats. Freely moving rats bearing cardiac cannulae were bled every 6 min for 3 h. During the first 90 min of bleeding, an equal volume of saline was injected after withdrawal of each blood sample, while during the second 90 min the replacement was done with saline containing naloxone at a dose of 0.5 (lower dose) or 1.0 (higher dose) mg/kg/h; statistical comparison was done between both treatment periods. In 4-week OVX rats, a significant increase in the mean LH level was observed through the 90-min period of lower-dose naloxone treatment, without significant changes in the pulse frequency and amplitude. In 4-week OVX rats treated with the higher dose and in 16-week OVX rats treated with either the lower or the higher dose, a significant elevation in mean LH levels was observed only during the first 30 min of treatment, which was probably related to the first, large LH peak in the naloxone treatment period. However, together with pulses appearing later in the treatment period, no significant changes were found in the LH pulsatility except for a decrease in frequency in 4-week OVX rats. In 32-week OVX rats, even the lower-dose naloxone did not induce an elevation in mean LH levels. The results demonstrate that naloxone can increase the LH secretion in the absence of ovarian hormones, and further that the effect on LH changes depending upon the dose of naloxone and the time after ovariectomy.

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“…GnRH release, also elicits a greater release of LH from young than from middle-aged females [28,29], although Wise et al [12] found no difference in LH concentration or pulse frequency between young and middle-aged ovariectomized rats given naloxone. Some of the decrease in pituitary responsiveness to GnRH may be the result of reduced pituitary GnRH receptors: middle-aged rats have fewer GnRH receptors during diestrus, and they show an attenuated increase in receptors in response to electrical stimulation of the medial preoptic area compared to young rats [30].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Attenuated Proestrous Luteinizing Hormone Surges in Middle-Aged Rats by Deconvolution Analysis1

Matt

Gilson

Sales

et al. 1998

Biology of Reproduction

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Reproductive aging in female rats is associated with attenuated preovulatory LH surges. In this study, detailed analyses of the episodic characteristics of the proestrous LH surge were conducted in young and middle-aged regularly cyclic rats. On proestrus, blood samples were withdrawn at 3-min intervals for 6 h and analyzed for LH concentrations by RIA in triplicate. Deconvolution analysis of immunoreactive LH concentrations revealed that there was no difference in the detectable LH secretory burst frequency between young and middle-aged rats. However, in middle-aged rats with an attenuated LH surge on proestrus, the mass of LH secreted per burst and the maximal rate of LH secretion per burst were only one fourth (p < 0.01) of those in young and middle-aged rats with normal LH surges. Furthermore, middle-aged rats with attenuated LH surges had a 4-fold decrease (p < 0.01) in the maximal rate of LH secretion per burst compared to young and middle-aged females with normal LH surges. The apparent half-life of endogenous LH was similar among the 3 groups. The attenuated LH surges of middle-aged rats were related specifically to a decrease in LH burst amplitude with no change in pulse frequency. The orderliness of moment-to-moment LH release as quantified by the regularity statistic, approximate entropy, was comparable in the 3 groups. Our findings of a markedly decreased amount of LH released per burst and preserved orderliness of the LH release process strongly suggest that a deficient GnRH drive and/or reduced responsivity to the GnRH signal, rather than altered timing of the signal, accounts for the age-related decline in reproductive function in female rats as presaged by an attenuated proestrous LH surge in middle age.

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Opioid Inhibition of Luteinizing Hormone Release Declines with Age and Acyclicity in Female Rats*

Cited by 16 publications

References 47 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

Naloxone Affects the Luteinizing Hormone Secretory Pattern in the Short- and Long-Term Ovariectomized Rat

Characterization of Attenuated Proestrous Luteinizing Hormone Surges in Middle-Aged Rats by Deconvolution Analysis1

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