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N J MacLusky

Publications and source records attributed to N J MacLusky.

At least 145 records · Page 8Linked to original sources
PubMed1979

Antiestrogen inhibits the induction of progestin receptors by estradiol in the hypothalamus-preoptic area and pituitary.

Estradiol treatment of ovariectomized-adrenalectomized rats produced an increase in cytosol progestin binding in the hypothalamus-preoptic area (HPOA), pituitary, and uterus. In the HPOA and pituitary, this induction of progestin receptors by estradiol was inhibited by the antiestrogen CI-628 under a variety of dose and time conditions. In the uterus, inhibition of the full effect of estradiol on progestin binding was observed after 3 days of injection of antiestrogen and estradiol. In the absence of estradiol, the antiestrogen produced a slight induction of progestin receptors in the HPOA and pituitary and a substantial induction of progestin receptors in the uterus. The results suggest that the induction of progestin receptors could be a key intermediate step in some behavioral and neuroendocrine actions of estradiol.

Animals↗
PubMed1977

Sex differences in the distribution of cytoplasmic oestrogen receptors in rat brain and pituitary: effects of gonadectomy and neonatal androgen treatment.

High affinity binding of 17 beta-oestradiol was measured in cytosols of hypothalamus, amygdaloid region, pituitary and (in females) uterus of adult male and female rats. There were no differences between intact or gonadectomised male and female animals in any of the tissues in the equilibrium dissociation constants (Kd). The number of available binding sites (n) in brain and pituitary in intact females at metoestrus is higher than at proestrus but only in hypothalamus is n greater than in ovariectomised animals. Binding sites in male hypothalamus, amygdala and pituitary are significantly less than in metoestrous females; the sex difference is seen also in gonadectomised rats but is significant only in pituitary. In all female animals the highest concentration of binding sites in the hypothalamus is in the anterior part and the lowest in the posterior part. The distribution of binding sites and Kd values in adult females treated neonatally with testosterone propionate were not different from those of intact proestrous rats. In intact males the highest level of n was in mid-hypothalamus; after gonadectomy the pattern reverted to that in females. It is suggest that these results support the concept that testicular androgen is conversted in brain to a substance with affinity for cytosol oestrogen receptor.

Amygdala↗
PubMed1975

An androgen receptor in rat brain and pituitary.

Dihydrotestosterone (DHT) binding was measured in cytosols from brain regions and pituitary of adult female rats and, with the addition of ventral prostate, in adult male rats. Two types of binding were distinguished: one, saturable at concentration of DHT greater than or equal to 5 X 10(-9) M and an unsaturable component. In intact males saturable (limited capacity) binding was detected only in ventral prostate cytosol; 3 days after orchidectomy the saturable binding sites increase 3-fold in prostate and in pituitary, hypothalamus, amygdala and cortex to detectable levels in approximately the same abundance as in females. There were significant differences in the affinities of the limited capacity binding reactions in cytosols of different tissues though all were in the order of magnitude, 10(-9) M DHT. The affinity in pituitary cytosol was lower than in brain regions with the single exception of female amygdala in which the affinity was significantly lower than in cytosol of the same region from 3-day castrate males. The specificity of the limited capacity binding was investigated by competition between [3h]DHT and unlabelled steroids; the most effective competitors were potent androgen agonists and antagonists.

Amygdala↗
PubMed1975

Physiological variation in abundance of oestrogen specific high-affinity binding sites in hypothalamus, pituitary and uterus of the rat.

High-affinity binding of [2,4,6,7-3-H]oestradiol-17 beta has been studied in cytosols prepared from hypothalami, pituitaries and uteri of female rats killed at different stages of the oestrous cycle, and in cytosols prepared from the hypothalami and pituitaries of male rats. In all cases the equilibrium dissociation constant of reaction was of the order of 10- minus 10 mol/1. The number of available high affinity sites per tissue (n) varied with physiological state. In females, n fluctuated with the oestrus cycle. In hypothalamus and pituitary, n fell by about 60 and 40% respectively in pro-oestrus, replenishment occurred during oestrus but could be delayed by phenobarbitone administration during the afternoon of pro-oestrus. In the uterus, n varied biphasically, there being peaks during dioestrus and oestrus, and troughs at pro-oestrus and metoestrus. The numbers of available sites at metoestrus were 12-5 times 10-9, 10-6 times 10-10 and 24-4 times times 10-10 for hypothalamus, pituitary and uterus respectively. In male rats, values for n were similar to those obtained for females at pro-oestrus (n/hypothalamus equals 6-8 times 10-9, n/pituitary equals 4-2 times 10-10). Binding was oestrogen specific in all the tissues studied.

Animals↗
PubMedDate not supplied

Concentration of [16 alpha-125I]iodoestradiol in human ovarian tumors in vivo and correlation with estrogen receptor content.

The gamma emitting estrogen [16 alpha-125I]iodoestradiol was administered to 11 patients with ovarian cancer and 1 patient with endometrial cancer. At specific times after the administration of the tracer, portions of the tumor and of control tissues, fat and muscle, were removed and counted. The amount of radioactivity in these tissues was compared to the cytosolic estrogen receptor content of the tumor, measured by Sephadex LH-20 gel filtration, in biopsy specimens taken before the injection of the tracer. There was a strong correlation (p less than 0.005) between the estrogen receptor concentration in the biopsied tumor and the amount of radioactivity in the tumor. There was no correlation between the isotope in the muscle and the tumor receptor, nor between the radioactivity in the tumor and that in fat or muscle. As would be expected for a steroid receptor mediated process, the bulk of the total tissue radioactivity was present in the nuclear compartment of the tumors. This pattern was not observed in the muscle. Furthermore, the nuclear radioactivity in the tumors was positively correlated with the cytosolic estrogen receptor content. These experiments demonstrate that under in vivo conditions this gamma emitting estrogen is concentrated in tumors in a manner that is dependent upon the estrogen receptor. It was also found that the concentrations of radioactivity in the blood were high, producing low tumor to blood ratios. The blood level of isotope was not due to the presence of the unmetabolized steroid, which disappeared from blood rapidly, but was caused by circulating metabolites of the injected steroid. Since the concentration of the isotope in the tumor was dependent upon the estrogen receptor level, it would appear from these experiments that it is theoretically possible to use such compounds to image and monitor tumors that contain estrogen receptors. However, rapid metabolism would seem to preclude the use of 16 alpha-iodoestradiol itself for this purpose. These studies point to the possibility that the synthesis of analogs of 16 alpha-iodoestradiol, sterically protected against inactivation by rapid metabolism, may lead to a radiopharmaceutical agent that would be useful for imaging and monitoring estrogen receptor containing tumors.

Adult↗
PubMedDate not supplied

Aromatase activity in human ovarian cancer.

Eighty-four tumor samples from 70 women with primary ovarian cancer were assayed for cytosol estrogen (ERc) and progestin (PRc) receptor concentrations and aromatase activity. In addition, 22 of the tumors were studied for their response to the aromatase inhibitor, 4-OH-androstenedione, in a soft agar clonogenic cell assay system. Although aromatase activity was detected in almost all of the primary tumors, this enzyme was barely detectable in the majority of metastatic tumor samples. There was no significant correlation between aromatase activity and either the ERc or PRc content of the tumors, or tumor grade. Of 12 tumors grown successfully in the soft agar culture system, only 1 showed a substantial (greater than 50%) reduction in colony-forming efficiency after exposure to the aromatase inhibitor. These results suggest that local estrogen biosynthesis probably does not play an important role in the majority of epithelial ovarian tumors. However, there may be a small subset of estrogen receptor-positive tumors in which aromatase could provide a local growth stimulus.

Androstenedione↗
PubMedDate not supplied

Estrogen formation in the mammalian brain: possible role of aromatase in sexual differentiation of the hippocampus and neocortex.

Recent studies suggest that sex differences in cognitive function may involve effects of circulating androgens on the developing cerebral cortex and hippocampus. The mechanism of these effects is not understood. In rhesus monkeys, aromatase activity is present in the hippocampus and several areas of the cerebral cortex during late fetal and early postnatal life. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developing cerebral cortex and hippocampus may involve local estrogen-mediated effects similar to those responsible for differentiation of the hypothalamic mechanisms controlling reproductive function.

Animals↗