Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0262471 (ENT)
 5,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norethindrone (ENT), which is a representative in estrane series of progestogen, is not only strongly progestational but also estrogenic and in some cases, antiestrogenic. To understand progestational effect and antiestrogenic effect, the interactions of ENT on estrogen and progestogen receptors were studied in the uterine cytosol of white female rabbit. The 274,200 X G supernatant of uterine homogenate was used as cytosol. 3H-Estradiol, 3H-Progesterone, 3H-ENT or cold ENT were incubated with uterine cytosol at 4 degrees C for 2 hours. Results are as follows: 1. Sucrose gradient centrifugation [5 approximately 20% linear and 40,000 rpm (159,200 X G) for 16 hours at 4 degrees C]: ENT was bound to extrogen 8S receptor in immature rabbit uterus (Fig. 2 & 3), and to progestogen 8S receptor in estrogen primed rabbit uterus (Fig. 5). 2. Kinetic study, determined by dextran coated charcoal (0.001% dextran and 0.1% charcoal): (1) In the uterine cytosol of immature rabbit, 3H-estradiol-receptor binding was observed with Kd divide by 3.6 X 10-9 M and it was revealed that ENT was a competitive inhibitor to this binding with Ki divide by 2.6 X 10-6 M, as in Fig. 6. (2) 8S component, obtained by centrifugation of uterine cytosol (Fig. 1) in estrogen primed rabbit, binds 3H-progesterone with Kd divide by 8.1 X 10-10 M and Bm (maximal binding sites) divide by 5.0 X 10-8 M/mg of protein, and ENT was a competitive inhibitor in this binding with Ki divide by 2.3 X 10-9 M (FIG. 7 & 8). 3H-ENT-8S binding was demonstrated with Kd divide by 1.1 X 10-9 M and Bm divide by 8.7 X 10-8 M/mg of cytosol protein (Fig. 8). These results indicate: (a) ENT is bound to both estrogen and progestogen receptors in 8S macromolecules of uterine cytosol, (b) competitive inhibition of ENT to these bindings indicated that ENT is bound to these receptors at the steroid binding sites where estradiol and progesterone bind to, (c) ENT has much more affinity to progestogen receptor (Ki divide by 2.3 X 10-9 M) than to estrogen receptor (Ki divide 2.6 X 10-6 M), (d) while ENT is bound to progestogen and estrogen receptors at the same time, Bm of ENT (8.7 X 10-8 M/mg of cytosol protein) is more than Bm of progesterone (5.0 X 10-9 M/mg of cytosol protein), and Kd of ENT (1.1 X 10-9 M) was less than Ki of ENT (2.3 X 10-9 M) in the binding to progesterone-receptor. Biologically, while ENT is bound to progestogen -receptor with high affinity and to estrogen receptor with low affinity, ENT is actually progestational in low dose and antiestrogenic in high dose but the anti-estrogenicity seems to be incomplete in vivo as ENT may be metabolized to a potent estrogenic compound, ethinyl estradiol
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PMID:[Interaction of norethindrone on estrogen and progesterone receptors in the rabbit uterine cytosol (author's transl)]. 18 90

Maternal behavior (ultrasound-induced pup-searching and retrieving) was studied in eight groups of female house mice with various hormonal backgrounds, experience with pups and function of the olfactory system. In their brains, estrogen receptor immunoreactive (ER-IR) cells were localized and quantified. All animals of all groups had ER-IR cells in a 'reliable subset' of brain areas, the medial preoptic area (MPOA) and ventromedial (VMH) and arcuate nucleus (ARH) of the hypothalamus. In another subset of brain areas, the anterior hypothalamic area (AHA) and cortical (CA) and medial (MA) amygdaloid nucleus, ER-IR cells can be expected in at least some animals of all experimental groups ('expected subset'). In a variable subset of additional brain areas (bed nucleus of the stria terminalis, BNST; suprachiasmatic nucleus, SC; lateral septal nuclei, LS; paraventricular nucleus of the hypothalamus, PVH; entorhinal and piriform cortex, ENT, PIR; subiculum, SUB; hippocampus, HPC; periventricular gray of the midbrain, PVG), ER-IR cells occurred only in some animals of some groups. Numbers of ER-IR cells in a given brain area, volumes occupied by these cells, and cell densities varied considerably among the groups. A covariation of cell counts and volumes was significant for most brain areas indicating that increases of numbers of ER-IR cells relate mainly to volume increases within a given brain area. Experience with pups correlated with an increase of ER presence in the AHA, VMH, ENT, PIR, SUB, HPC and PVG, however, only in the presence of estrogen. Estrogen and pup-experience together led to an increased ER presence in mainly the VMH, ENT and PIR, however, only in females with intact olfaction. Full maternal behavior (retrieving, ultrasound recognition) occurred after the high pregnancy- or experience-induced ER content was reduced to lower levels. The ER occurrence in lactating and experienced virgin females differed, however, in the AHA, BNST, SC, PVH, ENT, PIR, SUB, HPC and PVG showing that the maintenance of maternal behavior can run under different profiles of ER content in the brain. Ovariectomy and/or prolonged high blood-estrogen levels correlated significantly with decreased levels of ER-IR cells in most brain areas which could not be increased by pup-experience.
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PMID:Estrogen-receptor occurrence in the female mouse brain: effects of maternal experience, ovariectomy, estrogen and anosmia. 778 30

Estrogens are potent neuroprotective compounds in a variety of animal and cell culture models, and data indicate that estrogen receptor (ER)-mediated gene transcription is not required for some of these effects. To further address the requirement for an ER in estrogen enhancement of neuronal survival, we assessed the enantiomer of 17beta-estradiol (ENT-E(2)), which has identical chemical properties but interacts only weakly with known ERs, for neuroprotective efficacy. ENT-E(2) was both as potent and efficacious as 17beta-estradiol in attenuating oxidative stress-induced death in HT-22 cells, a murine hippocampal cell line. Further, ENT-E(2) completely attenuated H(2)O(2) toxicity in human SK-N-SH neuroblastoma cells at a 10 nM concentration. In a rodent model of focal ischemia, 17beta-estradiol (100 microgram/kg) or ENT-E(2) (100 microgram/kg), injected 2 h before middle cerebral artery occlusion, resulted in a 60 and 61% reduction in lesion volume, respectively. ENT-E(2), at the doses effective in this study, did not stimulate uterine growth or vaginal opening in juvenile female rats when administered daily for 3 days. These data indicate that the neuroprotective effects of estrogens, both in vitro and in vivo, can be disassociated from the peripheral estrogenic actions.
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PMID:The nonfeminizing enantiomer of 17beta-estradiol exerts protective effects in neuronal cultures and a rat model of cerebral ischemia. 1114 3