Evidence of 5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol and of 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol in the anterior pituitary of the prepuberal male rate]

Incubation of 3H-5 alpha-androstane-3 beta, 17 beta-diol with anterior pituitaries from immature male Rats led to the major production of polar radio-metabolites. Of these, 53 and 27% were identified with 5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol and 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol, respectively. The formation of these trihydroxysteroids may be involved in the intracellular regulation of 5 alpha-androstane-3 beta, 17 beta-diol levels.     

Changes in placental permeability to corticosterone and estradiol-17beta toward the end of gestation in the rat

Radioactivity in the fetal plasma 1 h after maternal injection of 14C-4-corticosterone or 14C-4-estradiol-17 beta on day 21 of gestation was markedly higher than that 1 h after injection on day 22. Radioactivity in the maternal plasma was not different on these 2 days. The results suggest that the placental permeability to steroids from the mother to the fetus declines toward the end of gestation in the rat.     

Conformational dynamics of the beta2-microglobulin C terminal in the cell-membrane-anchored major histocompatibility complex type I

We have recently described an anti-beta2-microglobulin (beta2-m) monoclonal antibody (mAb 14H3) capable of recognizing the epitope 92-99 of the protein in the monomeric native state as well as in the fibrillar polymeric state, but not in the major histocompatibility complex type I (MHCI) anchored to the cell membrane. In the present study, we investigated the molecular basis for the inaccessibility of the C-terminal end of beta2-m in the MHCI complex, and demonstrated that mAb 14H3 binds the soluble fraction of the MHCI complex with a Kd of 0.3 microM. An interaction between the complex and the membrane protects beta2-m from immunological recognition at the MHCI level. This protection from antibody recognition can be weakened by procedures such as heat shock or gamma irradiation that perturb the membrane structure and commit the cell to the apoptotic pathway. mAb 14H3 can recognize MHCI in a transient state that most likely precedes beta2-m shedding and may be proposed as a useful tool for dynamic analysis of MHCI conformational modifications.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 micrograms of 18-OH-DOC dissolved in 0.5 ml of a 4:1 saline Cremophor-EL solution were injected i.v. A decrease of 55.7 +/- 6.1% in the amplitude of the EPs was observed with the hormone 16.3 min +/- 2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min +/- 6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Demonstration of a receptor for 5 alpha-androstane-3 beta, 17 beta-diol in the cytosol of the anterior pituitary of prepubertal male rats]

The presence of a specific receptor for 5alpha-androstan-3beta, 17beta-diol (3beta-diol) in the pituitary cytosol from prepubertal male rats was demonstrated. Its characteristics were: Ka = 5.2.10(7) M-1 KD = 1.9 X 10(-8) M, number of specific binding = 8.7 10(-14) moles per mg of proteins. Its sedimentation constant was 3 S. Competition assays showed that only 3beta-diol itself and estrogens were able to compete for the binding sites for 3beta-diol. Androgens, including 3alpha-diol, were inefficient. This receptor was found only in pituitary cytosol, it was missing from hypothalamic or cortical cytosols. This special localization seemed to foreshadow a specific role for 3beta-diol in the anterior hypophysis.     

Effect of synthetic ACTH (beta 1-23 corticotropin) on gestation and parturition in rats]

Daily administration of synthetic ACTH (betaI-23 corticotrophine) from day 15 of pregnancy induces delay or inhibition of parturition in normal or ovariectomized Rats injected or not with estradiol. Parturition takes place at approximatively normal time, when ACTH is stopped and estradiol continued. Radio-immunological assays show an increase of blood progesterone level after ACTH administration in castrated, but not in castrated and adrenalectomized Rats. Mechanisms of ACTH action are discussed.     

Inhibition of corticotropic function by administration of GABA in carp (Cyprinus carpio L.)]

The intracardiac injection (50 microgram/g) of GABA to Carps clearly inhibits the rise of the plasma cortisol level which occurs usually in response to the blood sampling manipulations. The inhibition starts thirty minutes after injection and lasts till the end of the experiment two hours later. The hypothesis that this neurotransmitter has a regulatory function on the corticotrop cells, especially on the excretion of ACTH has to be considered.     

Role of adenosine A1 and A2 receptors in the regulation of aldosterone production in rat adrenal glands

To investigate the roles of adenosine A1 and A2 receptors in the regulation of aldosterone production, we examined the effects of adenosine and adenosine agonists (N6-cyclohexyl adenosine; selective adenosine A1 receptor agonist and 5'-N-ethylcarboxamine adenosine; selective adenosine A2 receptor agonist) on aldosterone and cyclic AMP production in rat adrenal capsular cells. Neither adenosine nor 5'-N-ethylcarboxamine adenosine caused significant effects on basal aldosterone or cyclic AMP production. Also, adenosine (10(-3) M) showed no consistent effects on aldosterone and cyclic AMP production induced by ACTH. On the other hand, N6-cyclohexyl adenosine exhibited a significant inhibition of basal aldosterone and cyclic AMP production at doses of 10(-4) M and 10(-3) M; furthermore, 10(-3) M N6-cyclohexyl adenosine inhibited aldosterone and cyclic AMP production stimulated by ACTH. These results suggest that adenosine A1 receptors are coupled to and inhibit adenylate cyclase and may be involved in the inhibition of aldosterone production.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

Maternal and fetal corticosteroids in the sow at the end of gestation]

Foetal and maternal blood samples are taken on the sow at the end of pregnancy. No variations in maternal cortisol are found, but plasma cortisol levels in the foetus, which are relatively constant between days 70 and 100 of pregnancy (10 to 20 ng/ml), increase suddenly at the end of pregnancy reaching a mean of 210 ng/ml at birth. This high increase of foetal corticosteroids at birth, similar to that found in other species (ewe, goat, etc.), probably plays a role in the mechanisms releasing parturition. It also permits us to understand the action of ACTH which induces premature birth when given to the pig foetus in the last days of pregnancy.     

Evidence for the extranuclear localization of thymosins in thymus.

A new radioimmunoassay has been developed for thymosin beta 4 by generating rabbit polyclonal antibodies against the synthetic N-terminal peptide fragment 1-15 coupled to KLH. The synthetic analogue [Tyr12]-thymosin beta 4 (1-15) was used as tracer. This radioimmunoassay, with a useful range of 10-1000 pmoles, showed cross-reactivity with the second homologous beta-thymosin of man and rat (thymosin beta 10) but not of calf (thymosin beta 9). This radioimmunoassay, together with an improved radioimmunoassay for the N-terminus of parathymosin alpha, was employed for the measurement of the levels of thymosin beta 4 and parathymosin alpha in nuclear and extranuclear extracts of calf thymus. The bulk of these polypeptides was found in the extranuclear material whereas only traces were observed in the nuclear environment, which indicates the extranuclear localisation of alpha- and beta-thymosins.     

Radioimmunologic assay of plasma corticotropin in the green frog, Rana esculenta L.]

In the green Frog (Rana esculenta) the plasma contains a polypeptide immunologically related to human and porcine corticotropins. A radiommunoassay capable of detecting 4.10-12 g hog ACTH has been used for a direct plasma ACTH assay in the Frog. Using this method, the ACTH rate was determined both in untreated frogs and in animals under various experimental conditions.     

Hyperglycemic effect in the rabbit induced by ACTH4-10

In the rabbit, a single i.v. administration of ACTH4-10 (130 micrograms/kg) induces hyperglycemia. As ACTH4-10 also induces hypocalcemia and inhibits insulin secretion, we suggest that hypocalcemia, inhibition of insulin secretion, and hyperglycemia, are closely related.     

Enzymatic basis for protection of fish embryos by the fertilization envelope

The mechanism by which the fertilization envelope (FE) is able to protect the embryo of fish until hatching is almost unknown, except for its function as a physical barrier. FE extract from activated or fertilized eggs of the fishSalmo gairdneri was demonstrated to contain enzyme activities using an agar plate enzyme assay. The enzymes apparently active were carboxymethylcellulase (cellulase; EC 3.2.1.4), laminaranase (endo-1,3(4)--glucanase; EC 3.2.1.6), carboxymethylchitinase (chitinase; EC 3.2.1.14), xylanase (endo-1,4--xylanase; EC 3.2.1.8), mannanase (mannan 1,2-(1,3)--mannosidase; EC 3.2.1.77), dextranase (EC 3.2.1.11), a protease and lysozyme (EC 3.2.1.17). The FE extract exerted an antifungal or fungicidal action on the fungusSaprolegnia parasitica, whereas an extract from the vitelline envelopes (VE) has no apparent enzyme activity nor antifungal or fungicidal action. Enzymes acquired by the FE through the cortical reaction may have an important defensive role, protecting the embryo against invaders or pathogens.     

Antigenic determinants of beta-LPH, beta-MSH, alpha-endorphin, ACTH and alpha-MSH revealed by anti-beta-endorphin in neurons of the human infundibular nucleus]

Comparison of adjacent serial sections of the tubero-infundibular region of Human adult hypothalamus demonstrates that the same perikarya, axons and terminals are stained both with anti-beta-endorphin and anti 17-39 ACTH antisera. The most immunoreactive of these neurons are also revealed with anti alpha-endorphin, anti alpha and beta-MSH, anti-1-24 ACTH and anti beta-LPH. These results suggest that neurons of the infundibular nucleus can store and probably secrete peptide similar to propiocortin or fragment(s) of this molecule.     

Regulation of the type III InsP3 receptor and its role in beta cell function

The type III inositol 1,4,5-trisphosphate receptor (InsP3R) is an important intracellular calcium (Ca2+) release channel in the pancreatic beta cell. Pancreatic beta cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca2+. Both extracellular Ca2+ and Ca2+ mobilized from InsP3-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting beta cell line, preferentially express the type III InsP3R. These cells have been useful in determining the regulatory properties of the type III InsP3R and the role of this isoform in an intact cell. The type III InsP3R is ideal for signal initiation because high cytoplasmic Ca2+ does not inhibit its activity. Altered insulin secretion, the result of changes in Ca2+ handling by the beta cell, has significant clinical consequences.     

New histochemical contributions to the study of corticotropic cells in the adenohypophysis of the chick enbryo.]

Comparative analysis of results obtained after subsequent treatments of chick embryo adenohypophysis by anti-ACTH 17-39 Is, PAS and Bodian method demonstrates that ACTH cells are PAS positive, Bodian negative and are located in the cephalic lobe. With the histochemical fluorescence method of Falck, the cells marked by anti-ACTH 17-39 Is exhibit an induced fluorescence, after L-DOPA injection. However, after treatment by metopirone, numerous cells of the caudal part of the adenohypophysis take up L-DOPA but they are not corticotrophs.     

Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death

Pancreatic beta cell damage caused by pro-inflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) is a key event in the pathogenesis of type 1 diabetes. The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNγ-induced signaling and prevents diabetes in the non-obese diabetic mouse. Here, we investigated if SOCS-1 overexpression in primary beta cells provides protection from cytokine-induced islet cell dysfunction and death. We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1β, IFNγ, TNFα. However, it decreases the activation of caspase-3, -8 and -9, and thereby, promotes a robust protection from cytokine-induced beta cell death. Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNγ in beta cells. In summary, we show that interference with IFNγ signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death.     

An analysis on the predictability of CAPM beta for momentum returns

This paper demonstrates that the forecasted capital asset pricing model (CAPM) beta of momentum portfolios explains a large portion of the return, ranging from 40% to 60% for stock‐level momentum, and from 30% to 50% for industry‐level momentum. Beta forecasts are from a realized beta estimator using daily returns over the prior year. Periods such as 1969–1989 have been found in earlier studies to contain abnormal profits from momentum trading; however, we show that these were spuriously generated by measurement error in systematic risk. These results cast further doubt on the ability of standard momentum trading strategies to generate abnormal profits.