Inhibition Of Hormones Research Articles

Anterior pituitary response to stress : time-related changes and adaptation

A wide array of physical and psychological stressors alter the secretion of anterior pituitary hormones. However, both the qualitative and the quantitative features of the stressors as well as its duration markedly influence the final endocrine response. In addition, among all anterior pituitary hormones, only ACTH and prolactin levels appear to reflect the intensity of the stress experienced by the animals. Although physical stressors show a somewhat specific neuroendocrine profile, the response of the pituitary-adrenal (PA) and sympathomedulloadrenal axes are common to almost all stressors. After an initial stimulatory effect of stress, an inhibition of all anterior pituitary hormones, except ACTH, can be found provided the stressor is intense enough. The mechanisms responsible for this biphasic response to stress are likely to be located at sites above the pituitary. When the animals are repeatedly exposed to the same stressor, some behavioural and physiological consequences of stress exposure are reduced, suggesting that the animals become adapted to the stimulus. This process has been also termed habituation. Among all the pituitary hormones, only ACTH and prolactin levels are reduced as a consequence of repeated exposure to the same (homotypic) stressor, although some negative results have been reported. However, it has been recently reported that subtle changes in the characteristics of the stressors or in their regularity can greatly influence adaptation, and these factors might explain failure to find adaptation of ACTH and prolactin in some works. Habituation of ACTH and prolactin, when observed, appears to be specific for the chronically applied stressor so that the potentiality of the PA axis and prolactin to respond to a novel (heterotypic) stressor can be preserved. In the case of the PA axis, an intact or potentiated response to a novel stressor is observed in spite of presumably negative feedback exerted by daily stress-induced glucocorticoid release and the high resting levels of glucocorticoids. This phenomenon has been termed as facilitation and can be unmasked alternating stress. Although with the exception of the PA axis, developmental aspects of anterior pituitary response to stress have been poorly studied, available data suggest that dramatic changes occur in some hormones during weaning, with some, but less profound, changes thereafter. Responsiveness to stressors appears to mature with age, but developmental patterns differ among the various anterior pituitary hormones.

Hormonal Control and Evolution of Alternative Male Phenotypes: Generalizations of Models for Sexual Differentiation

SYNOPSIS. An organism's phenotype results from an interaction of environment and genotype. Sex steroids play a role in translating sexual genotype into phenotype. The focus of this research has been to extend the model of sex steroid hormone action in sexual differentiation to individual variation in reproductive phenotype. The hypothesis generated, called the relative plasticity hypothesis, has been tested in a species with alternative phenotypes, tree lizards ( Urosaurus ornatus ). Such species are useful models for tests of these ideas because variation is extreme and easily studied. These tests have shown that permanent differentiation of the territorial and nonterritorial phenotypes is accomplished by hormonal mechanisms operating during early development. These are similar to organizational actions of hormones classically described for sexual differentiation. A unique finding of this work is that the adrenal hormone progesterone regulates differentiation of the two male types. Furthermore, the nonterritorial male tree lizard appears to conditionally switch tactics between sedentary satellite and nomadic behavior. Nomadic behavior is triggered under stressful environmental conditions. Nonterritorial tree lizards show greater inhibition of reproductive hormones following stress than do territorial tree lizards, suggesting that a differential sensitivity of reproductive hormones to stress is the endocrine basis of conditional tactic switching in this morph. This mechanism is similar to the classical activational effects of hormones. Together, these findings indicate that individual variation in sexual phenotype is produced by mechanisms similar to sexual differentiation. Further refinement of the models and integration with some evolutionary ideas is explored.

Lower sex hormones in men during anticipatory stress

Free cortisol, luteinizing hormone (LH), total testosterone and monoamines were measured in two successive nocturnal urine collections in 50 healthy men to assess the influence of anticipatory stress. The first collection (N-2) was two nights before and the second (N-1) was just on the night before a one-day experimental stressor consisting of participation in a one-day clinical research protocol. The mean cortisol level increased from 23.4 (N-2) to 66.6 micrograms (N-1), while mean LH level decreased from 2.68 (N-2) to 1.71 IU (N-1) and the mean testosterone level fell from 1.31 (N-2) to 0.70 microgram (N-1). There were no changes in monoamines. Inhibition of sex hormones is a relatively neglected area of stress research.

Principles of immunomodulation

Abstract Investigation into hormone antibody interactions have demonstrated that antibodies can inhibit or potentiate both exogenous and endogenous hormone activity, raising the possibility that the immune system can be used to improve animal production efficiency. This paper reviews the physiology of antibody-manipulated hormone activity in growth regulation, particularly in relation to hormone enhancement; possible mechanisms for such a phenomenon are discussed. Lastly, it is now clear that potentiation and inhibition of peptide hormones may occur in vivo and this is reviewed in terms of growth factor bioavailability. Parallels are made between this natural means of regulation with antibody-mediated regulation.

Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: A randomized, controlled trial

We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for patients with hepatocellular carcinoma (HCC). Eighty-five consequent, previously untreated HCC patients with inoperable disease, were randomized to receive the luteinizing hormone-releasing hormone (LR-RH)-analogue triptorelin and the antiestrogen tamoxifen (33 patients) or triptorelin plus the antiandrogen flutamide (23 patients), or only placebo (29 patients) in a double blind fashion. All groups were comparable as to age, sex, tumor extension, underlying cirrhosis and biochemical parameters. The tamoxifen (TMX) group had a significantly longer survival (282 days) compared with flutamide (112 days) and with placebo (127 days) groups ( P = .0238, log rank test). The upper quartile of patients in the TMX group lived 384 days or longer, and most of them (57.1%) were women ( P < .0005), in contrast to the upper quartile of the placebo (170 days, 16.7% women) and the flutamide group (134 days, 33.3% women). The calculated tumor volume doubling time (TVDT) was significantly higher in the TMX group (296 days) than in the other two groups (99 and 101 days for placebo and flutamide groups, respectively, ( P = .023). In a Cox proportional hazards model, the TMX treatment, along with the baseline Okuda's HCC stage, the hepatitis B surface antigen, the portal vein diameter, the carcino embryonic antigen (CEA) and a self-assessment score of quality of life, were covariates predicting survival. Although the degree of serum sex hormone suppression was not a significant predictor of survival, the interaction of female sex and TMX treatment, it was ( P = .0052). We conclude that TMX treatment significantly prolongs survival and the TVDT in unresectable HCC. The effect is most pronounced in female patients and is unrelated to sex hormone suppression.

Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: A randomized, controlled trial

We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for patients with hepatocellular carcinoma (HCC). Eighty-five consequent, previously untreated HCC patients with inoperable disease, were randomized to receive the luteinizing hormone-releasing hormone (LR-RH)-analogue triptorelin and the antiestrogen tamoxifen (33 patients) or triptorelin plus the antiandrogen flutamide (23 patients), or only placebo (29 patients) in a double blind fashion. All groups were comparable as to age, sex, tumor extension, underlying cirrhosis and biochemical parameters. The tamoxifen (TMX) group had a significantly longer survival (282 days) compared with flutamide (112 days) and with placebo (127 days) groups (P = .0238, log rank test). The upper quartile of patients in the TMX group lived 384 days or longer, and most of them (57.1%) were women (P < .0005), in contrast to the upper quartile of the placebo (170 days, 16.7% women) and the flutamide group (134 days, 33.3% women). The calculated tumor volume doubling time (TVDT) was significantly higher in the TMX group (296 days) than in the other two groups (99 and 101 days for placebo and flutamide groups, respectively, P = .023). In a Cox proportional hazards model, the TMX treatment, along with the baseline Okuda's HCC stage, the hepatitis B surface antigen, the portal vein diameter, the carcino embryonic antigen (CEA) and a self-assessment score of quality of life, were covariates predicting survival. Although the degree of serum sex hormone suppression was not a significant predictor of survival, the interaction of female sex and TMX treatment, it was (P = .0052).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Acting Somatostatin Analogues in Pancreatic Islet Cell Carcinoma

In secreting islet cell carcinoma, the long-acting somatostatin analogue, Sandostatin, reduces symptoms of endocrine secretion both by inhibiting peptide secretion and by acting on the target organs. It could be used during the initial evaluation of patients with such tumors and thereafter when the tumor cannot be found or is metastatic. Its efficacy depends upon the tumor type and probably the presence of somatostatin receptors on the tumoral cells. It could decrease with time, especially in VIPomas. Side effects are few and usually mild. Hypoglycemia attacks in insulinoma could be worsened during treatment by the complete inhibition of hyperglycemic hormones. The inhibition of tumoral growth, based on animal models, appears infrequent in clinical practice.

Gonadotropin-releasing hormone binding sites in human breast carcinoma.

Gonadotropin-releasing hormone analogs can cause regression of hormone-dependent breast carcinomas. These effects are thought to be mediated through the inhibition of gonadotropic and steroid hormones. These analogs may also act directly on the tumor because they are effective in treating breast cancer in some postmenopausal women. The presence of specific binding sites for gonadotropin-releasing hormone was demonstrated in human breast carcinomas by means of a novel approach of ligand immunoblotting. The results indicate a possible mechanism by which the peptide has direct effects on this tissue. These binding proteins were not detectable in non-neoplastic breast tissue.

Intereuption of pregnancy by barbiturates in albino rats

Barbiturates inhibit thelh surge and release of gonadotrophins (lh and fsh) and prolactin from the pituitary in rats and hamsters. In the present study administration of phenobarbital (7-5mg) or barbital sodium (20 mg) twice a day from day 8–11 interrupts the pregnancy in rats with little or no foetal survival. The ovaries and the uterus of these rats resemble those of non-pregnant rats when autopsied on day 20 of pregnancy. These results suggest that the failure of maintenance of pregnancy by barbiturate treatment may be due to the inhibition of luteotrophic hormones from the pituitary during the crucial period of pregnancy, resulting in the insufficient secretion and release of ovarian progesterone and also estrogen.

Sulphinpyrazone--induced decrease in renal function: a review of reports with discussion of pathogenesis.

SummaryTen reports arc reviewed, presenting a total of 2 1 cases of acutc renal failure, ascribed to sulphinpyrazone therapy, usually early after myocardial infarction. A minority of these patients had a sulphinpyrazone induced allergic acute interstitial nephritis. Although acute uric acid precipitation may play a pathogenetic role, the arguments in favour of this mechanism are not convincing. It is suggested that in some cases an inhibition of vasodilatory renal hormones (prostaglandins and/or kallikrein kinins) could mediate renal functional im pairmcnt. Renal function should be closely monito red in patients taking this drug.

Effects of somatostatin on the exocrine pancreas and the release of duodenal hormones

Using “the artificial beta cell,” previous studies have demonstrated that in insulin-dependent diabetics somatostatin reduces insulin requirements up to 70% and causes a marked flattening of the blood glucose curve after food intake. 1 Furthermore, in insulin-dependent diabetics somatostatin diminishes by 75%–100% rises in blood glucose after oral glucose, but did not influence glucose levels following intravenous glucose. 2 Since during the somatostatin infusion, a 30% reduction in splanchnic blood flow was observed, 2 the diminution of postprandial hypoglycemia following somatostatin seemed attributable primarily to a circulation-dependent delay in carbohydrate absorption. The fact that radioimmunoassayable somatostatin has been found not only in the stomach of the rat but also in the upper intestine, 3 in amounts comparable to those found in the hypothalamus, allow the assumption that somatostatin is a hormone in the gastrointestinal tract, coordinating the secretion of the other hormones. Recently, somatostatin-positive cells were shown to be present in the bottom of the intestinal crypt by immunohistochemical methods; 18 these cells were distinguished from those in other organs by the presence of a cytoplasmic process reaching the gut lumen (external environment). The assumed physiological importance of somatostatin or a somatostatin-like substance in the alimentary tract is emphasized by the fact that recently 4 a somatostatin-like immunoreactive peptide was isolated from the porcine duodenum. It has been known for many years that various gastrointestinal hormones exert an influence on the blood flow of the gastrointestinal tract. 5,6 It is unclear whether the effect of somatostatin on the splanchnic blood flow can be explained by the inhibition of various gastrointestinal hormones. The fact that in insulin-dependent diabetics somatostatin did not improve the intravenous glucose tolerance but only the peroral one suggests that the different effects of somatostatin in the gut may be partly the result of inhibition of various duodenal hormones. The present studies were undertaken to characterize the influence of somatostatin on the release and the biological activities of the two classic intestinal hormones, secretin and pancreozymin.

Relation between the drug-metabolizing activities of liver microsomes and multiplicity of cytochrome P-450 (author's transl)

Wada et al. found a hyperbolic curve in the Lineweaver-Burk plots of the drug-metabolizing activity and competitive inhibition of steroid hormones to drugs, and suggested that several enzymes acting on different sites of various steroid hormone molecules might metabolize drugs without having specificities for hydroxylation sites. Recently, several cytochrome P-450s were separated and purified from liver microsomes. We studied the relation between the drug-metabolizing activities and multiplicity of cytochrome P-450 with the pH curve and the Lineweaver-Burk plots. Phenobarbital- and methylcholanthrene-treatment had remarkable effects on the pH curve of aniline hydroxylation by mouse liver microsomes. Addition of cortisol inhibited aniline hydroxylatin by liver microsomes from phenobarbital-treated mice more effectively at higher pH range and the pH curve was similar to that seen for normal mice. Haugen and Coon separated preparations [A] [B] and [C] with hydroxylapatite chromatography and we obtained [A'] (eluted by 100 mM K-phosphate buffer, pH 7.4) between [A] (50 mM) and [B] (300 mM). The preparation [A'] had the same absorption maximum (451 nm) of reduced CO complex as [A], but Km and pH curve for [A'] were similar to those for [B]. Each separated preparation of cytochrome P-450 showed a hyperbolic curve in Lineweaver-Burk plots and a different pH curve from each other.

Estrogens and ovarian follicular functions in Rana pipiens

Ovulation and oocyte meiotic maturation (germinal vesicle breakdown) occur following the in vitro exposure of amphibian ovarian follicles to progesterone or gonadotropic hormones. The effects of estrogens on these two processes, and the separation of the follicular membranes from the oocyte, alone or in combination with these stimulatory hormones, were simultancously assessed. Estrogenic hormones did not initiate ovulation, maturation, or membrane separation and exhibited no inhibitory effects on ovulation, maturation, or membrane separation induced with progesterone. Estrone was inhibitory to pituitary-stimulated ovulation, maturation, and membrane separation when added to the incubation media at the same time as the pituitary hormone. Ovarian follicles were insensitive to the inhibitory effects of estrone if the addition of the steroid was delayed several hours after exposure to pituitary hormones. Follicular insensitivity to estrone occurs prior to germinal vesicle breakdown. These data suggest that estrogens act to prevent the synthesis or release of pituitary-stimulated ovarian intermediate(s). The ovarian folliele wall rather than the oocyte appears to be the site of estrogen inhibition of gonadotropic hormones.

Implications of contraception. A. Metabolic effects of oral contraceptives.

Oral contraceptives have a variety of metabolic effects in many women who use them. They interfere with at least 3 reproductive processes. The primary effect appears to be inhibition of gonadotropin hormones. The second major antifertility action is on the endometrium. The third contraceptive effect which is on the cervix prevents alterations in cervical mucus that normally occur at ovulation permitting the ascent of sperm into the uterine cavity. The effects of oral contraceptives depend on: 1) the specific agent(s) employed; 2) the amount of the agents; 3) the proportion between agents; 4) the route of administration; 5) the length of time the patient has used the agent; and 6) the patients age. 1 of the best known metabolic effects of oral contraceptives is their ability to modify carbohydrate metabolism. Increased insulinogenesis occurs with both short-term and long-term use and may be related to a parallel effect on growth hormone levels and to increases in blood pyruvate and lactate. Contraceptive steroids increase the levels of plasma cortisol and decrease the clearance rate of its urinary metabolites. They have also been associated with liver function changes and blood pressure changes. It is not possible to state with certainty which alterations in function if any have a permanent effect on the health of women.

Status of Research on the Physiologic Control of Fertility

The status of research on the physiologic control of fertility is reviewed. Each of the steps for both male and female reproduction is vulnerable to interference. Inhibition of ovulation can be produced by inhibiting gonadotropin secretion. Norethynodrel and norethisterone are 2 preparations which offer effective contraceptive control when taken regularly. These compounds may inhibit spermatogenesis as well but have the side effect of inhibiting androgenic hormone thus reducing potentia and libido. Inhibition of gonadotropic action on the gonads can be accomplished in animal experimentation with Lithospermum ruderale extracts. Investigation of the biologic activity of the extracts are in progress. Immunologic procedures for contraception include use of antibodies to agglutinate substances in semen formation of antibodies against germ cells and immunochemical inhibition of reproductive hormones. Interference with early development of the zygote is possible with MER-25 an analogue of a synthetic estrogen Tace. Early experiments indicate it is possible to destroy eggs before the leave the fallopian tubes. M-xylohydroquinone prevents nidation by its effect on the endometrium. Interference with embryonic development after nidation can by accomplished with folic acid inhibitors which block normal amino acid incorporation in protein synthesis. Spermatogenesis can be inhibited with nitrofurans which however have unpleasant side effects. Alkylating agents effect spermatogenesis. Application of heat to testes will also interupt spermatogenesis. Interference with sperm passage is effected through vasectomy. This operation may prove an acceptable contraceptive method if its reversibility can be increased.

AN ANALYSIS OF AMENORRHEA BY THE USE OF COMMERCIAL PROLACTIN AND THE LUTEINIZING HORMONE1

The production of an inhibition of the estrous cycle in the rodent has been reported repeatedly with the use of various hormones as well as with other agents. The mechanism is obviously complicated, for anestrus may be produced through the inhibition of the gonadotropic hormones or it may occur as a result of a direct action upon the ovary itself. This phenomenon is of clinical interest since it may explain one of the causes of functional amenorrhea in the human, and indicate its proper treatment. On the other hand, if the mechanism can be sufficiently understood it may prove of value in the treatment of uterine hemorrhage of functional origin by enabling one to produce a temporary amenorrhea when it is desired. It is our purpose in this communication, therefore, to present what we believe may possibly be one of the fundamental factors concerned in the production of amenorrhea. It is an established fact that a large number of patients who lactate following parturition have periods of amenorrhea varying fr...