Relationship between Circulating Estrogens and the Central Mechanisms by which Ovarian Steroids Stimulate Luteinizing Hormone Secretion in Aged and Young Female Rats*

Lu, John; Gilman, Dennis P.; Meldrum, David R.; Judd, Howard L.; Sawyer, Charles H.

doi:10.1210/endo-108-3-836

Cited by 103 publications

(49 citation statements)

References 21 publications

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“…Although it is well known that the circulating level of estrogen decreases as a part of the normal aging process in women and female rats (Lu et al, 1981;Lamberts et al, 1997) and that the actions of estrogen change with age, the effects of aging on ER-β that play an important role in mediating estrogenic actions are poorly understood. Therefore, in the present study, we analyzed age-related changes in ER-β expression in the female rat brain at the transcriptional level under the physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the expression of ER-β mRNA in the female rat brain

Yamaguchi

Yuri

2007

Brain Research

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Estrogen is important for numerous physiological actions, most of which are mediated via the nuclear estrogen receptors (ERs), ER-α and ER-β, which modulate the transcription of target genes following estrogen binding. Estrogen functions change with age. In the present study, to reveal the effects of normal aging on ER-β expression in the brain, we examined ER-β expression at the transcriptional level using young (10 weeks), middle-aged (12 months) and old (24 months) intact female rats. In situ hybridization using a digoxigenin-labeled RNA probe was used to assess the number of ER-β mRNA-positive cells in each region in whole brain. ER-β mRNA-positive cells were detected throughout the brain in young female rats and were reduced in number in the olfactory bulb, cerebral cortex, hippocampus, accumbens nucleus, part of the amygdala and raphe nucleus of middle-aged rats, but did not decline further in number in aged animals. By contrast, the number of ER-β mRNA-positive cells was decreased in the hippocampus, caudate putamen, claustrum, accumbens nucleus, substantia nigra and cerebellum was not significantly different between young and middle-aged rats, but was decreased in old rats. These results indicate that the expression of ER-β mRNA in the female rat brain is differentially modulated during aging and that the changes are region specific.Section: 2) Nervous System Development, Regeneration and Aging

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Section: Introductionmentioning

confidence: 99%

Age-related changes in the expression of ER-β mRNA in the female rat brain

Yamaguchi

Yuri

2007

Brain Research

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“…The positive feedback action of estrogen in ovariectomized rats on the LHRH level in mediobasal hypothalamus and LH secretion is attenuated in old rats (Steger et al, 1983;Wise, 1984). The positive feedback effect of progesterone in estrogen-primed ovariectomized rats on LH secretion is also attenuated (Gosden and Bancroft, 1976;Lu et al, 1977;Lu et al, 1981). Thus, alterations in the LH secretory mechanism in old female rats are apparent and are partly due to the alteration in norepinephrine secretion in the hypothalamus with age (Simpkins et al ., 1977;Wise, 1982aWise, , 1984.…”

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confidence: 99%

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

1990

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Age-related changes in hypothalamic luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) secretion were studied in young (6 months), middle-aged (12 months) and old (18 months) female rats. The LHRH levels in the mid-hypothalamic area were higher in intact middle-aged and old females than in young ones.Additionally, there was no age difference in the hypothalamic LHRH levels in male rats. In order to clarify the significance of this age-related increase in female rats, we examined the effects of progesterone treatment in estrogen-primed ovariectomized young and old rats on the LHRH levels in the median eminence (ME) and on plasma LH levels. We found phasic changes in ME-LHRH and plasma LH levels in estrogenprimed rats following progesterone treatment in rats of both ages, but the progesterone-induced change in ME-LHRH levels tended to be delayed in old rats compared with young females.This delay may correspond to the delayed onset, slow and low magnitude of plasma LH increase in old females. The ME-LHRH levels were generally higher in old rats than in young rats. Nevertheless, we found that the increase in plasma LH in response to progesterone treatment in estrogen-primed ovariectomized females was smaller in old rats than young rats.These results suggest that the LHRH secretory mechanism changes with age in female rats.Such alterations may result in the accumulation of LHRH in the mid-hypothalamic area and an increase in ME-LHRH.

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“…A circadian rhythm in LCGU in the SCN of young male rats (17) has been reported. We studied ovariectomized estradiol-treated young and middle-aged rats because (i) diurnal surges of LH occur in young ovariectomized estradiol-treated rats with precise and predictable timing (14,18,19), (ii) the timing and amplitude of these surges are altered in middle-aged rats entering the transition to reproductive acyclicity (14,20), and (iii) age-related changes in steroid-induced LH surges are associated with changes in the rhythm of turnover of at least some neurotransmitters (13)(14)(15). Therefore, we hypothesized that if the timing of several neural events in the SCN were altered with age, middle-aged rats would show a change in the circadian rhythm of glucose utilization in the SCN.…”

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confidence: 99%

Aging alters the circadian rhythm of glucose utilization in the suprachiasmatic nucleus.

Wise

Weiland

et al. 1988

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

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We examined the possibility that alterations in the timing of cyclic luteinizing hormone (LH) release during the middle age transition to infertility reflect differences in the circadian pattern of neural function in pacemaker areas of the hypothalamus, particularly the suprachiasmatic nucleus. We measured local cerebral glucose utilization (LCGU) because this parameter is an index of local brain function. We assessed LCGU in several brain areas of young and middle-aged ovariectomized estradiol-treated rats since LH surges are altered when rats are middle-aged. This alteration is correlated with changes in the diurnal pattern of neurotransmitter turnover in several hypothalamic areas that regulate cyclic LH release. The data demonstrate a circadian rhythm in glucose utilization in the dorsal and ventral suprachiasmatic nucleus. In young rats, LCGU increases within 1 hr of lights-on, increases further just prior to the initiation of the LH surge, and decreases within 1 hr oflights-off. In contrast, middle-aged rats show a more gradual increase in LCGU after lights-on, with no further increase prior to the LH surge, and a premature decrease during the afternoon and evening. The data suggest that changes in the circadian pattern of LCGU may be related to the alteration in timing and amplitude of estradiol-induced LH surges in middle-aged rats. Changes in the integrity of the biological clock or in the ability of the biological clock to entrain other neurochemical events may underlie the onset of altered cyclic reproductive function and the transition to irregular estrous cyclicity.The female reproductive system provides a unique model system to investigate mechanisms regulating endocrinedependent aging processes because changes that lead ultimately to infertility and the disappearance of reproductive cycles occur relatively early during adulthood. Thus, one can examine the regulation of aging processes in the virtual absence of age-related pathologies. The reproductive system of the aged female is characterized by the absence of both cyclic gonadotropin release and cyclic ovarian function. The period of total acyclicity and infertility follows a transitional phase during which ovulations occur at increasingly irregular intervals, the probability that a given cycle will be ovulatory is reduced, and the pattern of preovulatory gonadotropin surges and steroid hormone release is altered. Hypothalamic, pituitary, and ovarian functions are altered during the middleage transitional phase (1-4); however, the relative contribution of each to the transition to reproductive acyclicity is not well understood. The present study tested the hypothesis that a loss in precision of the circadian rhythm of hypothalamic function occurs during middle age, disrupting cyclic reproductive function.Reproductive cyclicity has a circadian basis and depends on the integrity of a neural pacemaker (5-7). Everett et al. (5) proposed that, in rodents, the timing and regularity of preovulatory gonadotropin surges are governed by diurnal ne...

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Relationship between Circulating Estrogens and the Central Mechanisms by which Ovarian Steroids Stimulate Luteinizing Hormone Secretion in Aged and Young Female Rats*

Cited by 103 publications

References 21 publications

Age-related changes in the expression of ER-β mRNA in the female rat brain

Age-related changes in the expression of ER-β mRNA in the female rat brain

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

Aging alters the circadian rhythm of glucose utilization in the suprachiasmatic nucleus.

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