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M Haji

Publications and source records attributed to M Haji.

80 records · Page 5Linked to original sources

Age-associated changes in nuclear binding of rat uterine estradiol receptor complexes.

Nuclear binding of cytoplasmic estrogen receptors was measured in an in vitro cell-free system, using various mixtures of cytosols and nuclei from uteri of mature (6-9 month old) and senescent (24-25 month old) Wistar rats. Both nuclei and cytoplasmic receptors from senescent uteri were 25-35% less efficient in supporting nuclear binding than those obtained from mature tissues as evidenced by the concentrations of occupiable nuclear acceptor sites. No age differences in association or dissociation constants were observed for the nuclear binding reaction. However, the apparent inability of some aged receptors to bind to the full complement of mature nuclear acceptor sites may indicate a qualitative deficiency in the cytosols of senescent uteri.

Aging↗

Isolated uterine nuclei and cytosol receptors of aged rats exhibit impaired estrogenic stimulation of RNA polymerase II.

An in vitro cell-free system of uterine nuclei and cytosol receptors has been used to analyze the effects of aging on estrogen stimulation of RNA polymerase II activity. By using fixed concentrations of nuclei and cytoplasmic receptor--estrogen complexes (R-E2), it was found that mature nuclei are 3 times more efficient (155% vs. 57%) than old ones for stimulation of polymerase activity by mature R-E2. Meanwhile, mature R-E2 are 5 times more efficient (155% vs. 31%) than old ones in supporting such stimulation in mature nuclei. Stimulation by old cytosol R-E2 is so poor that it is essentially unaffected by nuclear age (31% with both mature and old nuclei). Finally, equimolar mixtures of mature and old cytosol R-E2 stimulate polymerase II activity in mature nuclei by 77%, a value intermediate between mature and old cytosols used separately. These results indicate that both nuclei and cytosol from old uteri are deficient in their ability to support estrogenic stimulation of RNA polymerase II.

Aging↗

Excess in vitro prolactin secretion by pituitary cells from ovariectomized old rats.

Various in vivo and in vitro pituitary lactotropic and gonadotropic functions were measured in mature (6-7 mo, normally cycling) and old (24 mo, constant diestrus) female Wistar rats. Serum prolactin (PRL) levels were higher (P less than 0.001), whereas luteinizing hormone (LH) values were similar (P greater than 0.05) in old versus mature rats both before and 3 days after ovariectomy. Serum PRL levels decreased significantly (P less than 0.005) postovariectomy only in the mature rats. The in vitro release of PRL and LH was measured for 4 days in primary adenohypophyseal cell cultures from the ovariectomized rats. Both basal and 17 beta-estradiol (E2)-stimulated PRL release (P less than 0.001) and production (P less than 0.005) were greater by cells from old rats. In contrast, both basal release and E2-stimulated LH release were greater (P less than 0.001) by cells from mature rats. Peak PRL release by cells from both old and mature rats occurred after exposure to E2 doses 1/100th of those required for peak LH release. These data support the hypothesis that intrinsic derangements in anterior pituitary function contribute to the reproductive decline in aging female rats and that different pituitary cell types exhibit discordant age changes in estrogenic sensitivity.

Aging↗

Effects of in vivo estradiol administration on availability of rat uterine nuclear acceptor in measured in vitro.

Estradiol injected in vivo successfully completes for binding to uterine nuclear acceptor sites measured by the assay of Kon and Spelsberg (1). Such competition is time-and dose-dependent, with maximal inhibition (75%) 1 h after injection and at a dose of 10 micrograms of 17 beta-estradiol per 300 g of BW. Thus, this assay appears to accurately measure those uterine nuclear acceptor sites mediating estrogen action in vivo.

Animals↗

Effect of aging on prolactin regulation of rat striatal dopamine receptor concentrations.

Administration of highly purified rat prolactin by miniosmotic pump increases striatal dopamine receptor concentrations in both mature (4-6 months) and senescent (24 months) male Wistar rats. Although receptor levels in untreated rats are about 30% lower in the senescent group, elevated levels following prolactin are not significantly different between ages. Increases in circulating prolactin levels after 7 days of treatment were not detectable at the low concentrations used (150 ng/hr). In fact, there was a trend toward decreases in circulating prolactin concentrations to the same level in both groups after treatment, despite substantially elevated basal levels in many of the senescent rats.

Aging↗

Age-related changes in the concentrations of cytosol receptors for sex steroid hormones in the hypothalamus and pituitary gland of the rat.

Estrogen and androgen receptors were measured in cytosols from hypothalamus, pituitary and uterus or prostate of rats at 3 stages in life, from 90 to 650 days old in females and from 90 to 550 days old in males. Saturation analysis of cytosol 17 beta-estradiol receptors in females demonstrated a significant age-associated reduction in maximum binding capacity in hypothalamus and uterus already at 300-330 days of life, but there was no significant change in pituitary gland. However, there was no difference in binding affinity, steroid specificity, sedimentation coefficient, chemical nature and heat lability of cytosol 17 beta-estradiol binding of these tissues among the 3 age groups. In males, each receptor for 17 beta-estradiol, testosterone and 5 alpha-dihydrotestosterone was isolated by sucrose density gradient centrifugation from hypothalamic, pituitary and prostate cytosols. These receptors showed the same sedimentation coefficient of 8-9S in all age groups. Androgen binding by cytosols already decreased at 300-330 days of life, but estrogen binding was lower at 500-550 days of life than in younger adults. The increase in the serum luteinizing hormone level after gonadectomy was significantly depressed with aging in both females and males. These findings suggested that the age-associated reduction in cytosol sex steroid hormone receptors was ascribable to changes of numbers of binding sites. These age-related changes may be concerned with feedback system dysfunction of hypothalamic-pituitary-gonadal axis in aged rats.

Aging↗

Impaired estrogen stimulation of RNA polymerase II activity in uterine nuclei of senescent rats.

The effects of age on estrogen stimulated nuclear RNA polymerase II activity were studied in uteri of ovariectomized mature (6-8 months) and senescent (24 months) rats. Basal levels of RNA polymerase II activity were the same in both age groups. Following 17 beta-estradiol (E2) administration, RNA polymerase II activities increased at 6 h and reached a peak at 12 h in mature rats. In old rats, however, activities did not change until 12 h and reached a maximum at 18 h after injection. The effects of various E2 doses were examined at 6 h after injection. In mature rats, 1 microgram of E2 per 100 g body weight stimulated polymerase II activity, and maximum response was observed above 3 micrograms per 100 g. In senescent rats, this activity did not increase at doses below 3 micrograms per 100 g, but was stimulated by 10 micrograms of E2 per 100 g body weight to levels similar to those in mature rats. These results indicate that induction of uterine nuclear RNA polymerase II activity is delayed and less sensitive to E2 in old female rats than in their young counterparts.

Aging↗