Showing papers on "Adrenal cortex published in 1980"

Control of Adrenal Androgen Secretion

Abstract: I. Introduction The human adrenal cortex secretes a variety of androgens, as shown in Fig. 1, in addition to cortisol and aldosterone. Some of these steroids function as androgens, or serve as precursors for androgen or estrogen formation in peripheral tissues. The control of glucocorticoid and mineralocorticoid secretion is largely under the influence of ACTH and the renin-angiotensin system, respectively. However, the mechanism of control of adrenal androgen (AA) secretion is less well defined, and is the main subject of this review. II. ACTH, Dexamethasone and AAs ACTH is the most widely accepted modulator of AA secretion at present. Rosenfield et al. (1) studied endogenous cortisol and dehydroepiandrosterone (DHA) secretion in a normal volunteer and found a correlation between the rhythmicity of secretion of cortisol and DHA, although the magnitude of the DHA rhythm was much less than that of cortisol. Other investigators have administered bovine ACTH or synthetic forms such as the peptide-(l–24) cosy...

Pro-adrenocorticotropin/endorphin-derived peptides: coordinate action on adrenal steroidogenesis

Abstract: A synthetic peptide, representing a portion of the 16K (16,000 dalton)-fragment sequence within the pro-adrenocorticotropin/endorphin precursor molecule, potentiates the steroidogenic action of the 1 to 24 portion of adrenocorticotropin [ACTH(1-24)] on the rat adrenal cortex. The peptide has 27 amino acid residues and consists of gamma-melanotropin with a carboxyl terminal extension. It affects both the inner and outer adrenocortical zones of hypophysectomized animals, as evidenced by a synergistic augmentation of corticosterone and aldosterone production, respectively. The peptide can be distinguished from adrenocorticotropin by its activation of cholesterol ester hydrolase and its failure to stimulate cholesterol side-chain cleavage.

Maternal-Fetal Endocrinology

Abstract: Placental Synthesis of Steroid Hormones. Placental Polypeptides. Pregnancy-Related Changes in the Metabolism of Hormoes. Endocrine Pancreas and Mmaternal Metabolism. Hypertentsion in Pregnancy. The Renin. Angiotensin. Aldosterone System and Vasopressin. The Maternal Adenohypophysis. The Maternal Thyroid and Parathyroid Glands. The Maternal Adrenal Cortex. The Maternal Ovaries. Postpartum Lactation and Resumption of Reproductive Functions. The Human Fetal Hypothalamus and Pituitary Gland: The Maturation of Neuroendocrine Mechanisms Controlling the Secretion of Fetal Pituitary Growth Hormone, Prolactin, Gonadotropins, Adrenocorticotropin-Related Peptides and Thyrotropin. The Fetal-Maternal Neurohypophyseal System. The Fetal Adrenal. The Fetal Gonad and Sexual Differentiation. The Ontogenesis of Thyroid Function and Actions. Endocrinology of Implantation. Maintenance of Pregnancy and the Initiation of Normal and Premature Labor. The Influence of Hormones on Fetal Lung Develoment. Carbohydrate Metabolism: Insulin and Glucagon. Perinatal Mineral Metabolism. Newborn Adaptation: Adrenocortical Hormones and Adrenocorticotropic Hormone.

Immunofluorescence studies on autoantibodies to steroid-producing cells, and to germline cells in endocrine disease and infertility.

Abstract: This study was aimed at comparing the clinical significance of antibodies to steroid-producing cells with reactions to gonadal germline cells in patients with autoimmune polyendocrine diseases and isolated infertility or amenorrhoea respectively. Indirect immunofluorescence was used on human adrenal, ovary and testis. The gonad substrates were compared with rat, rabbit and monkey glands. 152 adrenal-positive sera were selected from 1030 that had been tested on adrenal cortex. Antibodies to steroid-producing cells in the gonads were found in fifty of these 152 selected cases and were studied in detail. When using human gonads as substrates, steroid-producing-cell antibodies were never detected in the absence of adrenal cortical immunofluorescence, though false-positive reactions were sometimes obtained on rat or rabbit gonads. Adrenal antibodies as well as those to steroid-producing cells were most frequent in Addisonian cases having one or more additional endocrine disease. The frequency of both types of antibody was lower in patients with Addison's disease and no other disorder but showing evidence of `polyendocrine serology'. Both antibodies were found least frequently when adrenalitis was unassociated with clinical or subclinical autoimmunity in other organs. We were able to confirm the immunofluorescence patterns described by other authors on adrenal gland and gonads, as well as the independent rise or fall in titre of these two types of antibodies in individual cases with time. Prolonged follow-up of forty-two Addisonian patients showed that adrenal antibodies disappeared in seven instances (17%). Ovum and sperm antibodies were found in about 25% of infertility cases and a smaller proportion of polyendocrine patients. Germline cell antibodies were rarely associated with other organ-specific reactions. In two cases, amenorrhoea was due to partial pituitary deficiency and the sera of the patients contained antibodies to pituitary prolactin-cells. Testicular `basement membrane' or `Sertoli-cell' immunofluorescence were each observed in isolated cases and are discussed in relation to known non-organ-specific and heterophile patterns. The significance of zona pellucida fluorescence in relation to blood group substances requires further study on human ova obtained by aspiration from mature Graafian follicles.

Adrenocortical response to corticotropin is potentiated by part of the amino-terminal region of pro-corticotropin/endorphin

Abstract: Five peptides derived from pro-corticotropin/endorphin (pro-ACTH/endorphin), the pituitary corticotroph cell prohormone, were bioassayed with isolated rat adrenocortical cells: alpha- and beta-melanotropin, beta-lipotropin, beta-endorphin, and the amino-terminal region of pro-ACTH/endorphin known as "16k fragment." The effect of each on steroidogenesis was measured at potentially physiological concentrations (0.01-1 nM) in both the absence and presence of varying concentrations of ACTH-(1-24). Of the peptides tested, only 16k fragment, the amino-terminal region of pro-ACTH/endorphin, has a slight but significant potentiating effect on ACTH-(1-24) action. Prior treatment of 16k fragment with trypsin for 30 sec dramatically increases this dose-dependent synergism. Experiments performed in vivo with hypophysectomized female rats indicate that the trypsin digest of 16k fragment stimulates cholesterol ester hydrolase (cholesterol esterase; sterol-ester acylhydrolase, EC 3.1.1.13) activity in the adrenal cortex but fails to activate cholesterol side-chain cleavage. The effect of the trypsinized material can therefore be qualitatively distinguished from that of ACTH-(1-24). When both ACTH-(1-24) and the digest are administered together, a synergistic increase in serum corticosterone concentration results. We propose that a portion of 16k fragment molecule may play a hormonal role in the control of adrenocortical steroidogenesis.

Immunocytochemical localization of the sex steroid-binding protein of plasma in tissues of the adult monkey Macaca nemestrina

Abstract: The sex steroid-binding protein (SBP) present in the serum of the monkey Macaca nemestrina is shown to exist in cells of tissue involved in reproduction. The localization was demonstrated by immunofluorescence with monospecific antibodies raised against homogeneous human SBP. These antibodies were previously shown to crossreact with monkey SBP. The protein appears to be located in the cytoplasm of epithelial cells lining the prostate alveoli, the ducti of the epididymis, and the seminiferous tubula of the testes of the monkey. The protein is also present in the cytoplasm of parenchymal cells of the liver, where SBP is believed to be synthesized, and in cells of the adrenal cortex, where steroids are known to be synthesized. Controls appear dark and illustrate specificity of the immunofluorescence, ruling out both tissue autofluorescence and other nonspecific interactions. In all cases, the relative intensity of fluorescence appears minimal in the nuclei of cells. Experiments performed with cultured MCF-7 cells indicate that SBP can across the plasma membrane and enter into the cytoplasm but not into the nucleus. Additional studies indicate that the monospecific antibodies do not crossreact with the monkey prostate androgen receptor, as shown by ultracentrifugation in sucrose densty gradients. The physiological significance of these observations is not known; however, the existence of this protein in cells of target tissues for sex steroids introduces a new dimension in our thinking about the role of this protein in androgen action.

Localization of calmodulin in rat tissues

Abstract: The localization of calmodulin, a calcium-dependent modulator of many enzymes, was studied in rat liver, skeletal muscle, and adrenal slices Calmodulin is found in liver cytoplasm, nucleus, and plasma membrane Much of the cytoplasmic calmodulin is associated with glycogen particles presumably bound to enzymes involved in glycogen metabolism Skeletal muscle calmodulin is found on the I-band, also associated with glycogen particles Intermyofibrillar staining that is not glycogen associated is also observed Calmodulin is localized in the cytoplasm and nucleus of adrenal cortex cells Injection of corticotropin leads to a greatly increased localization of calmodulin in nuclei of the adrenal cortex These observations suggest that one role of calmodulin may be the regulation of hormone effects on nuclear processes

Polypeptide hormone receptors in vivo: demonstration of insulin binding to adrenal gland and gastrointestinal epithelium by quantitative radioautography.

Abstract: A tissue-screening survey employing quantitative radioautography was carried out at 2 min after the intravascular injection of 125I-insulin into laboratory rats. The results revealed a substantial binding of insulin to cells forming the proximal convoluted tubule in kidney, hepatocytes of liver, acinar cells of the pancreas, parenchymal cells of the adrenal cortex and medulla, and epithelial cells of the gastrointestinal tract. Control experiments indicated that this binding was due to a specific interaction with the insulin receptor, except in the case of kidney where the binding was shown to be nonspecific. Although the major target for insulin action (liver) clearly demonstrated specific insulin binding, several other classical targets (adipocytes, skeletal, cardiac, and smooth muscle cells) showed no specific 125I-insulin binding and therefore indicated the limits of sensitivity of the in vivo radioautographic method. Nevertheless, the working hypothesis of a direct correlation of insulin receptor density with insulin action points to the hitherto unemphasized targets of pancreas, adrenal gland, and gastrointestinal tract as major sites of insulin action in the body.

Demonstration of Glucocorticoid Receptors in the Adrenal Cortex: Evidence for a Direct Dexamethasone Suppressive Effect on the Rat Adrenal Gland

Abstract: The adrenal cortex was evaluated for the presence of glucocorticoid receptors and functions. Substantial binding of [3H]dexamethasone was observed in aminoglutethimide-treated, hypophysectomized, and intact rats. Further studies demonstrated binding in cultured bovine adrenocortical cells and in Y-1 cells, a cloned murine cell line of adrenal cortical origin. Scatchard analysis of specific binding data in cytosol from hypophysectomized rats revealed an apparent Kd of approximately 15 nM and a receptor content (Nmax) of 123 fmol/mg cytosol protein. Analysis of Y-1 cell cytosol showed a Kd of approximately 17 nM and Nmax of 190 fmol/mg protein. The binding site in hypophysectomized rats had the following steroid specificities: high affinity for dexamethasone, corticosterone, and progesterone; moderate affinity for 11 beta-cortisol, and low affinity for testosterone, estradiol, pregnenolone, and 11 alpha-cortisol. Sedimentation in sucrose density gradients revealed 8S binding peaks in cytosols prepared from intact rat adrenal glands, Y-1 cells, and cultured bovine adrenocortical cells. Time- and temperature-dependent nuclear uptake of [3H]dexamethasone in Y-1 cells was demonstrated. In vivo treatment of hypophysectomized rats with dexamethasone significantly enhanced the rate of adrenal atrophy. ACTH stimulation tests in hypophysectomized rats showed a decreased corticosterone response in dexamethasone-treated rats compared to that in control animals. However, in vitro, there was no evidence for an effect of dexamethasone on ACTH-stimulated corticosterone production. The data indicate that the adrenal cortex possesses a high affinity binding site that fulfills the criteria for a glucocorticoid receptor. Glucocorticoid administration enhances adrenal atrophy and impairs adrenal function. We speculate that this action contributes to the suppressive effect of glucocorticoids on the pituitary-adrenal axis.

Characterisation of an adrenal zona glomerulosa-stimulating component of posterior pituitary extracts as alpha-MSH.

Abstract: The secretion of aldosterone from the zona glomerulosa of the mammalian adrenal cortex is stimulated by ACTH, potassium, angiotensin II and III, growth hormone, serotonin and E series prostaglandins1–7. Some experimental and clinical studies suggest that additional stimulants of the zona glomerulosa must exist, possibly including pituitary factors other than ACTH6,8–13. The possibility that posterior pituitary extracts may contain a zona glomerulosa stimulant was first suggested 20 years ago14,15, but has since received little attention. We describe here the purification from posterior pituitary extracts of activities that stimulate rat glomerulosa cells and whole tissue in vitro. One of the active compounds has been identified as α-MSH (melano-cyte stimulating hormone).

Ontogeny of the renin-angiotensin-aldosterone system in the fetal and newborn lamb.

Abstract: Thirteen chronic fetal lamb preparations between 95 and 142 days of gestation (term 145--150 days), and 10 newborn lambs were studied before and after the acute (1--2 min) infusion of furosemide (2 mg/kg). The baseline to peak plasma renin activity (PRA) response to furosemide increased from delta 3.0 +/- 1.3 ng/ml/hr (M and SEM) and 95--106 days of gestation to delta 18.4 +/- 4.0 (P less than 0.01) at 123--142 days and delta 33.6 +/- 6.5 (P less than 0.001) in the newborn. Baseline plasma aldosterone concentrations were similar in the fetus and pregnant ewe; aldosterone levels were higher in the newborn lamb than in the nonpregnant ewe. The newborn plasma aldosterone response to furosemide via the endogenous renin-angiotensin was delta 17.1 +/- 4.2 ng/dl (P less than 0.01); the fetal lamb plasma aldosterone level did not increase. The results indicate that the renin-angiotensin system cannot be stimulated by furosemide under 106 days of gestation; the response after 110 days increases with gestational age. Aldosterone concentrations in the fetal lamb are probably maintained primarily by the pregnant ewe and do not increase in response to endogenous renin stimulation as in the newborn.

Influence of exposure to moderate altitude on the plasma concentraton of cortisol, aldosterone, renin, testosterone, and gonadotropins.

Abstract: The influence of 11 days at moderate altitude (2,000 m) combined with exercise on plasma concentration of testosterone, FSH (follicle-stimulating hormone), LH (luteinizing hormone), cortisol, aldosterone, and renin activity was studied in ten healthy subjects. Within 48 h of arrival at moderate altitude a significant increase in testosterone was found whereas FSH had decreased significantly and LH showed a tendency to decrease. Cortisol increased significantly at the beginning and reached a maximum at the end of altitude exposure. The plasma aldosterone level rose continuously and on the last day of altitude was significantly elevated. Plasma renin activity showed a tendency to decrease. On return to low land all measured parameters returned to base line values within 2 days. The findings of increases in plasma levels of aldosterone and testosterone (and serum T3 and T4, as reported by others) are in contrast to the previously found decrease of urinary excretion of all these hormones. This appears to be a distinct dissociation of serum levels of adrenal (and thyroid) hormones from their urinary excretion. The observed increase in plasma aldosterone is probably mediated through ACTH and the rise in plasma potassium, since plasma renin activity showed an opposite trend. The rise in plasma testosterone is probably of adrenal origin since plasma gonadotropins declined simultaneously. The increase of plasma levels of glucocorticoids, mineralocorticoids, and androgens after an ascent from 600 m to 2,000 m above sea level is compatible with an ACTH-mediated stimulation of the entire adrenal cortex and/or a diminished elimination of adrenal steroids: The concomitant fall of FSH, LH, and plasma renin would then be a consequence of a direct negative feedback inhibition of these hormones.

A correlative study of the adrenal cortex in adreno-leukodystrophy--evidence for a fatal intoxication with very long chain saturated fatty acids.

Abstract: Thirty adrenal glands from patients with adreno-leukodystrophy (ALD) have been studied by light microscopy, three by enzyme histochemistry, three by electron microscopy and two by tissue culture. Cytoplasmic ballooning and striations result from proliferation of smooth endoplasmic reticulum and accumulations of lamellar-lipid profiles and clear clefts (crystalloids). Striated adrenocortical cells, the only pathognomonic adrenal lesion in ALD, display cytoplasmic lamellae, decreased amounts of rough endoplasmic reticulum and depression of several enzymes (alpha-glycerophosphate dehydrogenase, 3 beta-hydroxysteroid dehydrogenase and TPNH diaphorase). The striated cells also demonstrate decreased ability to adapt to changes in microenvironment, both in vivo and in vitro. A blunted response by striated cells to focal peripheral cytolysis leads to cytoplasmic erosion, atrophy and macrovacuoles. ACTH has a pivotal role in the evolution of these lesions. We propose that the pathognomonic lamellae of ALD basically represent bilayers or bimolecular leaflets of very long chain saturated fatty acids, while lamellar-lipid profiles and clefts contain cholesterol esterified to these abnormal fatty acids. The similarity of lamellar-lipid profiles of ALD to cytoplasmic lesions induced by long chain saturated fatty acids suggests that the very long chain saturated fatty acids isolated in ALD are cytotoxic and are responsible for adrenocortical cell dysfunction in this disease.

The Neuroendocrine System and Aging

Abstract: The course of aging in most endocrine glands is moderately well documented in man, but is somewhat less understood in the rat. With increasing age in man there is a significant decline in the secretion of hormones by the thyroid, adrenal cortex, testis and ovary; pituitary growth hormone falls but gonadotrophins rise. In man decline in the secretion of testicular and ovarian steroids appears to be due to primary age changes in the gonads, whereas in the rat age changes in the central regulatory mechanisms appear to be responsible for gonadal aging. Such findings have led to the formulation of a number of neuroendocrine theories of aging, which explain peripheral aging on the basis of an aging clock in the brain, primary age changes in neurotransmitter metabolism, age changes in the hypothalamus, pituitary and thyroid, or in the regulatory actions of these glands.

Parathyroid Hormone Acutely Increases Polyphosphoinositides of the Rabbit Kidney Cortex by a Cycloheximide-sensitive Process

Abstract: Parathyroid hormone(PTH) rapidly increases the concentrations of diphosphoinositide and triphosphoinositide in rabbit kidney cortex. Cycloheximide pretreatment abolishes these effects of PTH. These findings are similar to those reported for adrenocorticotropin and cyclic AMP action in the adrenal cortex, and suggest a common mechanism. Cycloheximide-sensitive effects of PTH, e.g., phosphaturia, may require polyphosphoinositides and/or other phospholipids.

Cytophysiology of the adrenal zona glomerulosa.

Abstract: Publisher Summary The mammalian adrenal cortex shows a clear histologic zonation: the outer subcapsular layer, the zona glomerulosa, consists of many cords of irregular-shaped cells arranged in various patterns according to the species examined. Zona glomerulosa cells possess the distinctive ultrastructural features of the steroid-producing cells: (1) mitochondria with tubular cristae, although in many species only lamellar or plate-like cristae are observed; (2) a well developed smooth endoplasmic reticulum (SER); and (3) some lipid droplets. However, there are some differences in morphology among the various species. In some mammalian species, a lipid-free layer between zona glomerulosa and zona fasciculata is described and named “zona intermedia.” The chapter reviews the fine structure and cytology of the normally functioning zona glomerulosa of various mammalian species. It also discusses the morphology of the zona intermedia cells.

Potassium and angiotensin II increase the concentrations of phosphatidic acid, phosphatidylinositol, and polyphosphoinositides in rat adrenal capsules in vitro.

Abstract: We examined the effects of K+ and angiotensin II, the major regulators of aldosterone secretion, on phospholipid metabolism during incubation of glomerulosa-rich, adrenal capsules. Addition of increasing amounts of K+ and angiotensin II to the incubation media elicited progressive increases in corticosterone production and capsular concentrations of phosphatidic acid, phosphatidyl-inositol, and polyphosphoinositides. These effects are similar to those previously reported for ACTH in the whole adrenal cortex. A common mechanism, i.e., activation of the phosphatidate-polyphosphoinositide cycle, may be operative in the action of steroidogenic agents in their target tissues.