Role of gonadal and adrenal steroids and thyroid hormones in the regulation of molting in domestic goose

Plasma levels of testosterone (T), 17-β-estradiol (E2), progesterone (P4), dehydroepiandrosterone (DHEA), corticosterone (B), thyroxine (T4) and triiodothyronine (T3) were monitored during postnuptial and the prenuptial molt in domestic goose (Anser anser domesticus) in both sexes. 1. At the beginning of postnuptial molt (when the old, worn dawny-, and cover feathers' loss starts) in ganders, the levels of T, E2, P4 decrease while DHEA and B significantly increase. The elevated levels of T4 and low T3 concentrations characteristic of the last phase of the reproduction, remain unchanged. In layers, similar changes were observed, however, B decreases. 2. In the early phase of outgrowth of wing and cover feathers, plasma levels of T, E2 and P4 are low. Elevated B, DHEA and T4 concentrations decrease in ganders, while in layers DHEA increases and B and T4 levels remain unchanged. T3 increases in both sexes. 3. The subsequent intensive outgrowth period of wing- and cover feathers both in ganders and in layers is characterized by very low levels of T, E2, DHEA and T4, but P4 increased, and T3 concentration remain high. 4. At the end of postnuptial molt - when the outgrowth of dawny, cover-, and wing feathers stops - very low T, E2, P4, DHEA and T4 levels and and high T3 plasma levels were found in both sexes. Fast increase of plasma B was detected in ganders, while in geese, B concentration remain high. 5. During prenuptial molting (outgrowth of contour and tail feathers) low E2, P4 and T4, increasing T and DHEA, but very high T3 and B plasma concentration were measured in ganders. In layers, very low T, E2, P4, DHEA and T4 levels, and very high B and T3 levels were found. 6. At the beginning of the fall-winter sexual repose (postmolting stage) T, E2, P4, DHEA and T4 levels increase, T3 and B declines in both sexes. 7. In the subsequent phase of fall-winter period (preparatory stage) there is a further increase in T, P4 and T4, a fast increase of B and a decrease of E2, DHEA and T3 in ganders. In layers, T, P4 and DHEA decrease, B increases and the T4 and T3 do not change. 8. At the beginning of reproduction high T level, unchanged DHEA, slightly declined P4, and decreased E2, T4, T3 and a strong decline of B concentrations occur in ganders. In layers, T is further increased, E2 and P4 shows high levels, and, at the same time DHEA and T3 remain unchanged, while B and T4 decrease.     

Interaction between ovarian and adrenal steroids in the regulation of gonadotropin secretion

Recent work from our laboratory suggests that a complex interaction exists between ovarian and adrenal steroids in the regulation of preovulatory gonadotropin secretion. Ovarian estradiol serves to set the neutral trigger for the preovulatory gonadotropin surge, while progesterone from both the adrenal and the ovary serves to (1) initiate, (2) synchronize, (3) potentiate and (4) limit the preovulatory LH surge to a single day. Administration of RU486 or the progesterone synthesis inhibitor, trilostane, on proestrous morning attenuated the preovulatory LH surge. Adrenal progesterone appears to play a role in potentiating the LH surge since RU486 still effectively decreased the LH surge even in animals ovariectomized at 0800 h on proestrus. The administration of ACTH to estrogen-primed ovariectomized (ovx) immature rats caused a LH and FSH surge 6 h later, demonstrating that upon proper stimulation, the adrenal can induce gonadotropin surges. The effect was specific for ACTH, required estrogen priming, and was blocked by adrenalectomy or RU486, but not by ovariectomy. Certain corticosteroids, most notably deoxycorticosterone and triamcinolone acetonide, were found to possess "progestin-like" activity in the induction of LH and FSH surges in estrogen-primed ovx rats. In contrast, corticosterone and dexamethasone caused a preferential release of FSH, but not LH. Progesterone-induced surges of LH and FSH appear to require an intact N-methyl-D-aspartate (NMDA) neurotransmission line, since administration of the NMDA receptor antagonist, MK801, blocked the ability of progesterone to induce LH and FSH surges. Similarly, NMDA neurotransmission appears to be a critical component in the expression of the preovulatory gonadotropin surge since administration of MK801 during the critical period significantly diminished the LH and PRL surge in the cycling adult rat. FSH levels were lowered by MK801 treatment, but the effect was not statistically significant. The progesterone-induced gonadotropin surge appears to also involve mediation through NPY and catecholamine systems. Immediately preceding the onset of the LH and FSH surge in progesterone-treated estrogen-primed ovx. rats, there was a significant elevation of MBH and POA GnRH and NPY levels, which was followed by a significant fall at the onset of the LH surge. The effect of progesterone on inducing LH and FSH surges also appears to involve alpha 1 and alpha 2 adrenergic neuron activation since prazosin and yohimbine (alpha 1 and 2 blockers, respectively) but not propranolol (a beta-blocker) abolished the ability of progesterone to induce LH and FSH surges. Progesterone also caused a dose-dependent decrease in occupied nuclear estradiol receptors in the pituitary.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of development and adrenal steroids in the regulation of the mineralocorticoid receptor messenger RNA.

The ontogeny, adrenal-feedback regulation and regional distribution of the mineralocorticoid receptor (MR) mRNA were examined in the rat brain and kidney. In the kidney, MR mRNA levels in the adult were only 25-30% of the neonatal concentration. Adrenalectomy caused a 35% increase in total brain MR mRNA and a 94% increase in kidney MR mRNA levels. Examination of the regional distribution of the MR mRNA within the brain revealed that the hippocampus had the highest levels, and the mRNA abundance increased after adrenalectomy. The administration of dexamethasone to intact animals resulted in a significant reduction of MR mRNA in the kidney of neonatal rats but not in the brain. These data indicate that there are developmental changes in MR gene expression in kidney and that adrenal steroids can modulate MR gene expression in both the brain and kidney.     

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.     

Endocrine regulation of cervical ripening in humans--potential roles for gonadal steroids and insulin-like growth factor-I

Cervical softening is crucial for a normal parturition and corresponds to remodeling of the dominating cervical extra cellular matrix (ECM). The onset of labor as well as cervical ripening is under hormonal control. To get further information about the endocrine regulation of term cervical ripening the following study was undertaken: cervical biopsies were obtained vaginally at elective caesareans, after normal vaginal delivery and after PGE2 or antiprogestin RU486. Biopsies from non-pregnant women served as controls. The concentrations of estrogen receptor (ER) and progesterone receptor (PR) protein were quantitated by EIA and the mRNA levels by solution hybridization. The ERalpha and beta were localized by immunohistochemistry, identified by RT-PCR and quantitated by solution hybridization. The co-localizations of CD45 (leukocyte antigen) and CD68 (macrophage antigen) were studied by immunohistochemistry. The cervical concentrations of ER and PR proteins decreased at term to 15 and 25%, respectively, compared to the non-pregnant levels. A further decrease was measured in the maximal ripened cervix at parturition. The mRNA levels were unchanged but IGF-I mRNA reached a maximum at term. ERalpha mRNA was significantly decreased until delivery, whereas ERbeta mRNA, like IGF-I; was maximum at term. By immunostaining ERbeta could be co-localized with CD45 leukocyte antigen and CD68 macrophage specific antigen. Oral administration of RU486 induced a significant increase in ER protein concentration, whereas PGE2 and spontaneous ripening did not. These findings indicate that cervical ripening is related to significant local hormonal changes.     

Role of gamma-MSH peptides in the regulation of adrenal steroidogenesis

Alpha-, beta- and gamma-melanocyte stimulating hormones (MSHs) are peptides derived from the ACTH precursor, pro-opiomelanocortin. All three peptides have been highly conserved throughout evolution but their exact biological function in mammals is still largely obscure. In recent years, there has been a surge of interest in alpha-MSH and its role in the regulation of feeding. Gamma-MSH by contrast has been shown to be involved in the regulation of adrenal steroidogenesis and also has effects on the cardiovascular and renal systems. This review will provide an overview of the role that gamma-MSH peptides play in the regulation of adrenal steroidogenesis.     

Endocrine and neurogenic regulation of the orphan nuclear receptors Nur77 and Nurr-1 in the adrenal glands.

nurr77 and nurr-1 are growth factor-inducible members of the steroid/thyroid hormone receptor gene superfamily. In order to gain insight into the potential roles of nur77 in the living organism, we used pharmacologic treatments to examine the expression of nur77 in the mouse adrenal gland. We found that nur77 and nurr-1 are induced in the adrenal gland upon treatment with pentylene tetrazole (Ptz; Metrazole). This induction is separable into distinct endocrine and neurogenic mechanisms. In situ hybridization analysis demonstrates that nur77 expression upon Ptz treatment in the adrenal cortex is localized primarily to the inner cortical region, the zona fasciculata-reticularis, with minimal induction in the zona glomerulosa. This induction is inhibitable by pretreatment with dexamethasone, indicating involvement of the hypothalamic-pituitary-adrenal axis in the activation of adrenal cortical expression. When mice were injected with adrenocorticotrophic hormone (ACTH), nur77 expression in the adrenal gland spanned all cortical layers including the zona glomerulosa, but medullary expression was not induced. Ptz also induces expression of both nur77 and nurr-1 in the adrenal medulla. Medullary induction is likely to have a neurogenic origin, as nur77 expression was not inhibitable by dexamethasone pretreatment and induction was seen after treatment with the cholinergic neurotransmitter nicotine. nur77 is also inducible by ACTH, forskolin, and the second messenger analog dibutyryl cyclic AMP in the ACTH-responsive adrenal cortical cell line Y-1. Significantly, Nur77 isolated from ACTH-stimulated Y-1 cells bound to its response element whereas Nur77 present in unstimulated cells did not. Moreover, Nur77 in ACTH-treated Y-1 cells was hypophosphorylated at serine 354 compared with that in untreated cells. These results, taken together with the previous observation that dephosphorylation of serine 354 affects DNA binding affinity in vitro, show for the first time that phosphorylation of Nur77 at serine 354 is under hormonal regulation, modulating its DNA binding affinity. Thus, ACTH regulates Nur77 in two ways: activation of its gene and posttranslational modification. A promoter analysis of nur77 induction in Y-1 cells indicates that the regulatory elements mediating ACTH induction differ from those required for induction in the adrenal medullary tumor cell line PC12 and in 3T3 fibroblasts.     

Role of adrenal steroids on the cardiac c-AMP response to isoprenaline in the rat

The effect of adrenalectomy on the basal cardiac c-AMP level and the elevated c-AMP level induced by intravenous administration of isoprenaline (10 mcg/kg) were determined by radio-protein assay. The basal cardiac c-AMP level was not altered by adrenalectomy. But the cardiac c-AMP responses to isoprenaline was significantly less in adrenalectomized rats, maintained with 1% sodium chloride solution for one week; this effect, however, disappeared when animals were maintained for 2 or 4 weeks. This could not be restored by acute administration of dexamethasone (100 mcg/rat). The possible reasons for these effects of adrenalectomy are discussed.     

Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat

Rat steroidogenic tissues take up cholesterol, and it has been suggested that this process plays a regulatory role in steroid hormone synthesis. To provide evidence for this hypothesis, we carried out studies in lipoprotein-deficient rats. Lipoprotein deficiency, achieved by treating male rats with pharmacological amounts of estradiol, led to profound lowering of plasma cholesterol (8 +/- 2 versus 54 +/- 4 mg/dl) and adrenal cholesteryl ester content (113 +/- 57 versus 747 +/- 108 micrograms/organ). Basal serum corticosterone levels were decreased by 50%, and the response to adrenocorticotropic hormone (ACTH) was totally abolished. Injection of high density lipoprotein (HDL) to estradiol-treated animals restored the response of corticosterone to ACTH. Comparable in vitro studies with adrenal cell suspensions obtained from lipoprotein-deficient rats confirmed the in vivo data. Measurement of [14C]acetate incorporation and uptake of both HDL- and low density lipoprotein (LDL)-cholesterol in these adrenal cells showed a progressive increase with the duration of estradiol treatment, and neither of these two phenomena was altered by ACTH. These results provide in vitro and in vivo evidence for the hypothesis that normal adrenal steroidogenesis depends upon cholesterol delivery from plasma. Furthermore, under the conditions studied, ACTH does not stimulate adrenal de novo cholesterol biosynthesis nor the uptake of either HDL- or LDL-cholesterol.     

Pre-parturition profile of steroids and prostaglandin in cows with or without foetal membrane retention

Retained foetal membranes in cattle is one of the most common complications associated to the reduction in milk yield and impaired fertility in dairy cattle. In order to determine some endocrine mechanisms controlling parturition and delivery of foetal membranes, plasma concentrations of steroids and prostanoids were determined in 20 healthy Holstein cows. Samples were taken within the interval of 5 days pre-parturition to 12h after calving. Progesterone (P4) levels were similar in cows with (PR) and without (NPR) placental retention. While the estradiol-17beta (E2) peak at parturition was lower in PR than in NPR cows, cortisol levels were greater in PR cows 12 and 24h pre-parturition. The Prostaglandin F2alpha metabolite (PGFM) levels were higher at parturition in NPR compared with the PR group, but 12h later, these levels in the PR group increased so that concentrations were greater as compared with NPR cows. The Prostaglandin E2 metabolite (PGEM), 24, 48 and 72 h pre-parturition, were higher in PR cows. However, the PGFM:PGEM ratio was greater in cows up NPR at all time when included, indicating the importance of higher levels of Prostaglandin F2alpha (PGF2alpha) than Prostaglandin E2 (PGE2) for normal placental delivery. In conclusion, placental retention was related to both estrogen and PGF2alpha deficiency, which may be a consequence of metabolic stress leading to PGE2 and maternal cortisol synthesis before parturition.     

A clonal genetic screen for mutants causing defects in larval tracheal morphogenesis in Drosophila

The initial establishment of the tracheal network in the Drosophila embryo is beginning to be understood in great detail, both in its genetic control cascades and in its cell biological events. By contrast, the vast expansion of the system during larval growth, with its extensive ramification of preexisting tracheal branches, has been analyzed less well. The mutant phenotypes of many genes involved in this process are probably not easy to reveal, as these genes may be required for other functions at earlier developmental stages. We therefore conducted a screen for defects in individual clonal homozygous mutant cells in the tracheal network of heterozygous larvae using the mosaic analysis with a repressible cell marker (MARCM) system to generate marked, recombinant mitotic clones. We describe the identification of a set of mutants with distinct phenotypic effects. In particular we found a range of defects in terminal cells, including failure in lumen formation and reduced or extensive branching. Other mutations affect cell growth, cell shape, and cell migration.