Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study describes the use of adult rats as a model to determine whether chronic estrogen treatment irreversibly alters the capacity of Sertoli cells to secrete androgen binding protein (ABP). Twenty-five adult rats were implanted with silastic tubing containing 17 beta-estradiol. After 1 month of estradiol the epididymides had regressed to 47 per cent of the weight of the epididymides in a control group. The amount of ABP in control epididymides was 9.9 fmol./mg. protein, whereas no ABP was detectable in those from rats treated with estradiol for 1 month. Serum testosterone levels had been depressed by 90 per cent. Estradiol treatment for 8 months resulted in a 60 per cent lower body weight and a 91 per cent decrease in testicular weight compared to control animals. During this period the epididymides regressed significantly. When Sertoli cells were cultured from the testes of the estradiol implanted rats, in spite of the dramatic changes which had occurred in the testes, within 4 days the cultured cells synthesized ABP in response to FSH and testosterone. Furthermore, the direct addition of estrogen at a concentration of 200 ng./ml. to rat Sertoli cell cultures failed to depress ABP below control levels. Thus, although estradiol depresses ABP synthesis in vivo, probably through its depression of both gonadotrophin secretion and testosterone biosynthesis, it has no direct effect on the Sertoli cells, and its long-term inhibition of ABP synthesis by an indirect mechanism is reversible.
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PMID:The effect of estrogen on Sertoli cell function. 681 68

The effect of pinealectomy (Px) on the development of steroid positive feedback on luteinizing hormone (LH) release was examined in female rats subjected to surgery at 10 days of age. Estradiol-progesterone injection decreased serum LH in sham Px or intact controls younger than 20 days, while a significant LH release was found at day 22; Px rats showed a steroid-induced LH depression only at day 16, a positive feedback being detectable at day 20, 2 days earlier than in sham Px or intact rats. Daily injections of 10-50 micrograms melatonin to intact rats disrupted the LH negative feedback response at day 20, and diminished steroid-induced LH release at day 24.
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PMID:Pinealectomy advances the time of development of steroid feedback on luteinizing hormone release in immature female rats. 710 19

Whole cell patch-clamp techniques were applied to cultured smooth muscle cells isolated from the longitudinal layer of the late pregnant rat myometrium. Effects of estrogens on Ca channels were examined. Inhibitory effects of beta-estradiol (1 microM) on Ca channel currents were recognized. The inhibitory effects of beta-estradiol depended on holding potentials. beta-Estradiol shifted the steady-state inactivation curve in the negative direction by 7 mV at mid potential (n = 9). Diethylstilbestrol, a synthetic estrogen, gave similar effects on Ca channel currents at lower concentration (2 microM) to those of beta-estradiol. Strong inhibitory effects on Ca channel currents were obtained by higher concentration (20 microM). Diethylstilbestrol shifted the steady-state inactivation curve in the negative direction by 7 mV at mid potential (n = 5). The results indicate that estrogens influence the voltage dependency and the whole cell conductance of Ca channels of pregnant rat myometrial cells. The acute effect of estrogens may cause both electrical and mechanical depression of myometrium.
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PMID:Effects of estrogens on Ca channels in myometrial cells isolated from pregnant rats. 784 Jan 61

This study demonstrates a significant impairment in the acquisition of conditioned avoidance responses in female rats during their estrus phase. Progesterone (PROG 5 mg) injected 6 h prior to the test, significantly enhanced the performance exhibited by rats at estrus, but not at diestrus. In ovariectomized rats, the acquisition of conditioned avoidance responses was similar to the exhibited during diestrus and this behavior was depressed by a single dose of estradiol benzoate (EB 2 micrograms) injected 48 h prior to the test. PROG antagonized the avoidance depression induced by EB, but it was not able to induce changes in the acquisition of conditioned avoidance response in ovariectomized rats without EB pretreatment. Estradiol appears to be the principal ovarian steroid modulating the acquisition of an avoidance task, whereas PROG seems to have a secondary role in this behavior, regulating the actions of estradiol on the brain. PROG failed to induce consistent changes in some spontaneous motor behaviors in intact and ovariectomized rats.
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PMID:Progesterone effects on the acquisition of conditioned avoidance responses an other motoric behaviors in intact and ovariectomized rats. 804 42

Oestradiol-17 beta causes relaxation of isolated coronary arteries and increases blood flow in several vascular beds in human beings and animals. Oestrogen replacement therapy is associated with a lower incidence of cardiovascular disease, but the acute effects of oestradiol-17 beta on myocardial ischaemia are unknown. We have studied the acute effect of sublingual oestradiol-17 beta on exercise-induced myocardial ischaemia in eleven women (mean age 58 [SD 8] years) with coronary artery disease. The women did two treadmill exercise tests on separate days; 40 min before the test they took sublingual oestradiol-17 beta (1 mg) or placebo, in random order. Plasma oestradiol-17 beta concentrations were confirmed to be higher after sublingual oestradiol-17 beta than after placebo (2531 [1192] vs 155 [168] pmol/L, p < 0.001). Oestradiol-17 beta increased both time to 1 mm ST depression (456 [214] vs 579 [191] s, p < 0.004; difference of medians 92 [95% CI 46-254]) and total exercise time (569 [249] vs 658 [193] s, p < 0.01; difference 54 [10-212]). Acute administration of oestradiol-17 beta therefore has a beneficial effect on myocardial ischaemia in women with coronary artery disease. This effect may be due to a direct coronary-relaxing effect, to peripheral vasodilation, or to a combination of these mechanisms. Oestradiol-17 beta may prove to be a useful adjunct to the treatment of angina in postmenopausal women with coronary heart disease.
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PMID:Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in women with coronary artery disease. 810 4

Oral therapy with natural or synthetic estrogens, like ethinylestradiol, suffers from low, suboptimally defined bioavailability and excess hepatic estrogen actions. N,N-alkylated and non-alkylated sulfamates of ethinylestradiol, estradiol and estrone overcome these deficiencies. Ovariectomized Wistar rats (n = 6-7/group) were orally treated for 7 days, and killed on day 8, plasma was gained on days 0, 4, and 8. Systemic estrogenicity was quantified by assessment of uterine weight, vaginal cornification, and measurement of gonadotropins by homologous RIA. Estrogenicity in the liver was analysed. Angiotensinogen was estimated by RIA of angiotensin-1 after incubation of EDTA-plasma with porcine renin. Total and high-density cholesterol were measured by enzymatic methods. Preliminary biotransformation studies were performed after oral administration of 10 micrograms, 5 microCi [2,4,6,7-3H]estradiol sulfamate. Ethinylestradiol led to distinct elevation of angiotensin-1 and dramatic depression of cholesterol fractions, reflecting hepatic estrogen effects, already at doses with marginal systemic effects. Estradiol and estrone had systemic and hepatic estrogenic activity at much higher doses only. Estrogen sulfamates had systemic estrogen activity 10-90-fold above that of their parent estrogen. Non-alkylated sulfamates of given estrogens were more active than N-alkylated ones. Elevation of systemic estrogen activity was always combined with a dramatic reduction of hepatic estrogenicity. Estradiol sulfamate had a 90-fold elevated systemic estrogen activity vs estradiol, but lacked hepatic activity including the 30-fold dose inducing vaginal response. Three hours after administration no unchanged estradiol sulfamate was detectable in plasma. Rather peaks, probably representing estradiol and estrone, were found. Estrogen sulfamates are considered prodrugs of their parent estrogen, which do not interact with any liver function during the first-pass. They represent a new strategy of oral hormone administration. Their main potential seems to be the systemic generation of natural estrogens when used in oral contraceptives.
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PMID:Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application. 854 Dec 36

In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.
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PMID:Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression. 865 28

Nine women who had undergone hysterectomy and oophorectomy and who previously suffered from severe premenstrual syndrome (PMS) were given estrogen and progesterone in a naturalistic single-blind paradigm. The 13-item Beck Depression Inventory, Spielberger State Anxiety Inventory, Menstrual Distress Questionnaire and the Daily Ratings Form of the Premenstrual Assessment Form were all given daily. Estradiol and progesterone concentrations were estimated. When results from all subjects were considered together, these measures were not correlated with hormonal status. However, individual subjects showed correlations between some symptom scores and serum progesterone concentrations. We conclude that women diagnosed as having PMS do not respond in a uniform fashion to ovarian hormones. Further quantitative studies are needed to relate these individual differences to the syndrome of PMS.
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PMID:Can one induce premenstrual symptomatology in women with prior hysterectomy and bilateral oophorectomy? 886 Aug 83

An oral d-fenfluramine neuroendocrine challenge test was carried out in 17 women with premenstrual depression and 14 controls, twice in each subject, once in the late luteal phase when mood change was likely to be at its worst (i.e. premenstrual) and once postmenstrually. Women weighing < 65 kg received 15 mg, the remainder 30 mg of d-fenfluramine. Although there was considerable individual variability, a substantial average prolactin response was observed in both groups but no phase, group or group x phase interaction effects were found. Oestradiol levels were significantly higher during the postmenstrual test but showed no relationship to prolactin response. Cortisol showed a more modest response to the drug and a phase effect was found, with cortisol increase being greater during the postmenstrual test in both groups. In contrast to earlier findings with i.v. L-tryptophan challenge, the present study failed to show any difference in neuroendocrine response between women with premenstrual depression and controls. These results suggest that 5-hydroxy-tryptophan2 receptor function is unaltered in perimenstrual mood disorder although other interpretations of the negative findings are discussed.
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PMID:The neuroendocrine response to d-fenfluramine in women with premenstrual depression. 898 66

Cardiovascular effects of estrogens and particularly that of estradiol involve protection of the heart against ischemia. These effects were believed to be mainly indirect, mediated via changes in the blood and blood vessels. In the present paper a direct action of estradiol on the heart is demonstrated. Estradiol stimulates (p < 0.001) the Na,K-ATPase activity of cardiac sarcolemmal membranes by stimulating in an allosteric manner, the activation of the enzyme by potassium. The latter activation involves also an increase in affinity to potassium of the potassium binding sites on the enzyme molecule, but remains without any effect on the capacity and KD value of specific ouabain binding to the Na,K-ATPase. Estradiol is also antagonizing the depression of Na,K-ATPase activity that may be caused by ischemia and it is stimulating (p < 0.01) the ouabain-sensitive uptake of 86Rb into the heart cells. Our results indicate, that in addition to the known indirect effects of estradiol on the heart, the hormone also stimulates the activity and improves the kinetics of interaction of cardiac sarcolemmal Na,K-ATPase with ATP as well as with Na+ and K+ ions. This direct action may also account for the cardioprotective effects of estradiol.
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PMID:Estradiol modulates the sodium pump in the heart sarcolemma. 940 52


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