Showing papers on "Adrenal cortex published in 1981"

Characterization of corticotropin receptors on adrenocortical cells

Abstract: The binding of corticotropin (ACTH) to receptors on isolated rat adrenocortical cells was investigated with the aid of [[125I]ITyr23, Phe2, Nle4]ACTH-(1-38) (125I-ACTH analog) which retained full biological potency and had a specific radioactivity of 1800 +/- 75 Ci/mmol. Binding was highly specific to adrenocortical cells, and the radioactive peptide was displaced by low concentrations of ACTH but not by other basic peptides. Binding was rapid, reversible, and linearly related to the number of cells. 125I-ACTH analog was not significantly degraded by incubation with the cells at 23 degrees C for 1 hr. Scatchard analysis of the binding was compatible with a single class of binding sites with Kd = 1.41 +/- 0.21 nM, and the number of sites was estimated to be 3840 +/- 1045 per cell. The binding curve was superimposable on the concentration-response curve for cyclic AMP. Small, but significant amounts of 125I-ACTH analog were bound at concentrations sufficient for maximal stimulation of steroidogenesis. For a series of ACTH analogs, the concentrations of the peptides required for half-maximal stimulation of cyclic AMP production were in excellent agreement with the concentration required for half-maximal inhibition of binding. These results suggest that the adrenocortical cells contain only one class of ACTH receptors and that stimulation of a small fraction of these receptors (less than 3%) is sufficient for maximal steroidogenesis.

Biopterin cofactor biosynthesis: independent regulation of GTP cyclohydrolase in adrenal medulla and cortex

Abstract: Guanosine triphosphate cyclohydrolase, the enzyme that is apparently rate-limiting in biopterin biosynthesis, is increased in adrenal cortex and medulla of rats treated with insulin or reserpine. Denervation and hypophysectomy block the increase in medullary and cortical enzyme activity, respectively, whereas cycloheximide presents the increase in both tissues. These results provide evidence for induction and regulation of guanosine triphosphate cyclohydrolase.

Gonadal autoantibodies in patients with hypogonadism and/or Addison's disease.

Abstract: The sera from 325 normal individuals, 21 patients with Turner's syndrome, 505 patients with insulin-dependent diabetes mellitus, 15 patients with unexplained ovarian insufficiency, nd37 patients with Addison's disease or serological evidence of adrenal autoimmunity were examined for the presence of gonadal autoantibodies by an indirect immunofluorescent techniqueusing sections of human testis. All 12 patients found to have gonadal autoantibodies also had adrenocortical autoantibodies. These autoantibodies were completely absorbed with powdered adrenal cortex and thus were “steroidal cell” antibodies (SCA), cross-reactive with a cytosolic antigen in the steroid-producing cells of adrenal cortex, placental syncytiotrophoblast, Leydig areas of testis, and theca interna/ granulosa layer of ovarian follicles. Sera with SCA had reduced titers of adrenal antibodiesafterrepeated absorptions with gonadal or placental tissues, suggesting that adrenal-specific autoantibodies were also present. Sera from patients wit...

Return of pituitary-adrenal function after adrenal enucleation or transplantation : diurnal rhythms and responses to ether

Abstract: Adrenocortical diurnal rhythms and responses to ether vapor were studied in rats 1, 3, and 5 weeks after bilateral adrenal enucleation, autotransplantation, or sham transplantation in order to 1) determine whether diurnal rhythms in the plasma corticosterone concentration and adrenal responsiveness to ACTH are dependent on innervation of the adrenals, 2) compare regeneration of function of transplanted and enucleated adrenals, and 3) investigate adrenal mass-related nonsteroidal inhibition of ether-stimulated ACTH secretion. Rats in both enucleate and transplant groups exhibited significant morning-evening differences in adrenal and plasma corticosterone concentrations and significant adrenocortical responses to ether 3 and 5 weeks, but not 1 week, after surgery. The morning-evening differences in corticosterone concentration occurred in the absence of significant morning-evening variation in the plasma ACTH concentration, supporting our previous finding of a diurnal rhythm in adrenal responsiveness to ACTH. The responsiveness rhythm cannot be dependent on adrenal nerves unless transplanted adrenals receive functionally specific reinnervation within 3 weeks. The processes of regeneration of function after enucleation and after transplantation are similar; there were no differences in plasma or adrenal corticosterone values between rats in enucleate and transplant groups at any time or under any condition tested. As regeneration progressed, plasma ACTH responses to ether declined in both enucleate and transplant groups in the absence of changes in plasma corticosterone feedback. These results support our previous finding of adrenal mass-related nonsteroidal suppression of ACTH responses to ether.

Regulation of the fetal human adrenal cortex: effects of adrenocorticotropin on growth and function of monolayer cultures of fetal and definitive zone cells.

Abstract: Monolayer cultures have been prepared from both definitive and fetal zones of the human fetal adrenal cortex. Cultures from each zone consist predominately of adrenocortical cells, as determined by a specific morphological retraction response to ACTH, and by ACTH-induced inhibition of DNA synthesis and cell proliferation. Cell growth was stimulated by fibroblast growth factor. ACTH stimulated steroidogenesis in cells from each zone with an ED50 of 0.4–1.0 run and at a maximal concentration of 5 nM. Short term stimulation of less than 24 h with ACTH produced a pattern of steroid secretion that was characteristic of the zone of origin. Definitive zone cultures produced both cortisol and dehydroepiandrosterone plus its sulfate (DHA/S), with cortisol production exceeding DHA/S production. Fetal zone cultures produced more DHA/S than cortisol. 3β-Hydroxysteroid dehydrogenase, Δ4,5-isomerase enzyme activity was 3-fold less in fetal than in definitive zone cultures. Long term stimulation of 1–4 days with ACTH, 8...

Circulating angiotensin II and adrenal receptors after nephrectomy

Abstract: Mineralocorticoid secretion is predominantly controlled by the octapeptide angiotensin II, which exerts trophic actions on the adrenal glomerulosa and acute regulatory effects on aldosterone biosynthesis. The trophic actions include stimulation of angiotensin II receptors and enzymes of the aldosterone biosynthetic pathway, with corresponding enhancement of the aldosterone secretory capacity of the adrenal gland. The positive regulatory action of angiotensin II on its adrenal receptors occurs with elevations of the circulating peptide concentration within the physiological range and probably contributes to the increased sensitivity of the adrenal during sodium deficiency. In this action, angiotensin II differs from other hormones which decrease their target-cell receptors. However, the increase in adrenal angiotensin II receptors following nephrectomy has been interpreted as evidence for a tonic down-regulating effect of angiotensin II on its adrenal receptors. To clarify these conflicting views we evaluated the effects of nephrectomy on adrenal angiotensin II receptors in relation to blood angiotensin II and plasma electrolyte levels. We show here that hyperkalaemia contributes markedly to the post-nephrectomy increase in adrenal angiotensin II receptors, and that circulating angiotensin II levels persist for an unexpectedly long period after nephrectomy, presumably due to tissue generation of the octapeptide.

The Metabolism and Mechanism of Action of Aldosterone

Abstract: ALTHOUGH the clinical importance of the adrenal cortex in the regulation of electrolyte balance had long been realized (1), it was not until the early 1950s that the major regulatory steroid, aldosterone, was isolated and identified by Simpson et al. (2). Simpson and Tait used a sensitive mineralocorticoid bioassay based on changes of urinary 24Na/42K ratios in adrenalectomized rats to help isolate aldosterone (3). Aldosterone is still the most potent mineralocorticoid known: 30–50 times more potent than deoxycorticosterone and at least a thousand times more active than the glucocorticoids, cortisol and corticosterone. Aldosterone's greater potency is balanced by a reduced secretory rate compared with most other adrenal steroids (4, 5). Its synthesis, exclusively by the zona glomerulosa of the adrenal cortex, is responsive to dietary sodium and potassium manipulations and more acutely to ACTH, plasma potassium concentrations, and the renin-angiotensin system (5, 6). Many of the initial investigations were...

The 21-Hydroxylase Activity in the Glomerulosa and Fasciculata of the Adrenal Cortex in Congenital Adrenal Hyperplasia*

Abstract: In the two clinical syndromes of congenital adrenal hyperplasia due to a 21-hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18-hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17-deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect.

Evidence for a higher molecular weight precursor of cholesterol side-chain-cleavage cytochrome P-450 and induction of mitochondrial and cytosolic proteins by corticotropin in adult bovine adrenal cells

Abstract: Adult bovine adrenal cortical cells in monolayer culture were used to study the induction of cholesterol side-chain-cleavage cytochrome P-450 by corticotropin (ACTH). In the presence of 1 microM ACTH, there was a 4-fold increase in cortisol production by these cells over a 72-hr period and a corresponding increase in total cytochrome P-450 content. The incorporation of [35S]methionine into a number of cellular proteins was stimulated by the presence of ACTH in the culture medium, whereas the incorporation into other proteins was decreased. The temporal profile of these changes varied from one protein to another. Examination of the incorporation of [35S]methionine into mitochondrial protein showed an increased production of a radiolabeled protein that comigrated with the form of cytochrome P-450 known as side-chain-cleavage cytochrome upon incubation with ACTH. Thus, it appears that the cytochrome P-450scc content is increased in bovine adrenal cortical cells exposed to ACTH. Cytochrome P-450scc, synthesized in a cell-free translation system directed by RNA isolated from bovine adrenal cortical tissue or from cells, had a molecular weight of 54,500. Cytochrome P-450scc isolated from bovine adrenal mitochondria had a molecular weight of 49,000. Thus, cytochrome P-450scc is synthesized as a larger precursor that must be processed by proteolytic cleavage before or upon insertion into the mitochondrion.

Tetrahydrobiopterin increases in adrenal medulla and cortex: a factor in the regulation of tyrosine hydroxylase.

Abstract: Tetrahydrobiopterin, the cofactor for tyrosine hydroxylase and other monooxygenases, is present in tissues at apparent concentrations much less than those necessary to saturate the corresponding enzymes. Reserpine treatment or insulin-induced hypoglycemia in rats produces a statistically significant increase in the tetrahydrobiopterin content of both the adrenal medulla and the cortex. Adrenal denervation and hypophysectomy selectively block the increases in cofactor level in medulla and cortex, respectively, while cycloheximide prevents the increase in both tissues. Reserpine did not increase cofactor levels in liver, kidney, or corpus striatum but decreased that of the pineal gland. These results suggest that tetrahydrobiopterin is under neural control in the medulla and hormonal control in the cortex and that increases in cofactor may result from induction of enzyme(s) in the biosynthetic pathway. These results demonstrate regulation of tissue tetrahydrobiopterin and are consistent with the suggestion that cofactor levels participate in the regulation of tyrosine hydroxylase in the adrenal medulla and may have a function, as yet undetermined, in the adrenal cortex.

Parathyroid Hormone and Adenosine-3′,5′-Monophosphate Acutely Increase Phospholipids of the Phosphatidate-Polyphosphoinositide Pathway in Rabbit Kidney Cortex Tubules in Vitro by a Cycloheximide-Sensitive Process*

Abstract: Parathyroid hormone (PTH) rapidly increased the concentrations of phosphatidic acid, phosphatidylinositol, diphosphoinositide, and triphosphoinositide during incubations of rabbit kidney cortical tubules in vitro. These effects were preceded by increases in cAMP, which also induced virtually identical increases in these phospholipids. Pretreating the tubules with cycloheximide inhibited these phospholipid effects of PTH and cAMP. These findings are similar to those reported for ACTH and cAMP in the adrenal cortex. Hormones that utilize cAMP as their ”second messenger“ may influence membrane structure and function via stimulation of the phosphatidate-polyphosphoinositide pathway.

The effect of biofeedback-assisted relaxation training on blood pressure and selected biochemical parameters in patients with essential hypertension

Abstract: The effect of EMG biofeedback-assisted relaxation on blood pressure and selected biochemical parameters was evaluated in 38 patients with essential hypertension. Training consisted of 8 weeks of biofeedback and home practice of relaxation exercises. Mean blood pressure decreased in the experimental group from 144/90 to 133/84 mm Hg while the control group remained unchanged. Statistically significant decreases in the experimental group also occurred in muscle tension levels, in plasma aldosterone, and in urinary cortisol. Both aldosterone and cortisol are secreted by the adrenal cortex. It was concluded that the technique taught to the experimental group produced a reduction in skeletal muscle tension and a decrease in stress responding mediated by the adrenal cortex.

Glucocorticoid-induced lymphocyte death

Abstract: Glucocorticoids are the principal steroid hormones produced by the inner zones of the adrenal cortex. The natural glucocorticoids, present in amounts which vary according to species, are Cortisol and corticosterone. Corticosterone is generally about half as active as Cortisol. Dexamethasone, prednisolone, triamcinolone acetonide and certain other synthetic analogues of glucocorticoids which are widely used therapeutically and experimentally have some advantages over the natural hormones with regard to both activity and specificity. Dexamethasone, for example, is 10 to 100 times more active than Cortisol, has about 10 times higher affinity for glucocorticoid receptors, and is a ‘purer’ glucocorticoid in the sense that it cross-reacts much less with mineralocorticoid receptors. Cortisone and prednisone, once thought to be glucocorticoids, are now known to have no activity in themselves but to require conversion, respectively, to Cortisol and prednisolone (cf. Munck and Leung, 1977).

Functional differences between the outer and inner zones of the guinea pig adrenal cortex

Abstract: The guinea pig adrenal cortex is grossly composed of two regions: an outer, yellow zone and an inner, brown zone. These zones,which represent 33% and 66% of the total adrenocortical volume,respectively,can be separated by blunt dissection. It has been previously reported that specific pregnenolone and pregnenolone sulfate binding proteins are present in the high speed supernatant fraction (cytosol) prepared from the whole adrenal cortex of the. guinea pig. However, when cytosol was prepared from the separate outer and inner cortical zones, it was found that the steroid-binding proteins were concentrated in the inner zone. This correlated with the level of pregnenolone which was significantly greater in the cytosol of the inner zone where greater than 50% was found to be bound. In contrast, the concentration of cortisol was 30 times greater in the cytosol of the outer cortical zone and less than 4% was found to be bound. These data suggest that cortisol is produced primarily in the outer cortical zone, a e...

Aldosterone action in target epithelia.

Abstract: Publisher Summary This chapter provides the historical introduction to aldosterone The aldosterone biosynthesis by the zona glomerulosa of the adrenal cortex is controlled by a number of factors including the reninangiotensin system, plasma potassium, and, to a lesser degree, adrenocorticotropic hormone (ACTH) In cases of unrelenting release of aldosterone or administration of mineralocorticoids, a renal compensatory mechanism known as “escape” ensues The escape involves recruitment of those factors that are responsible for volume-related natriuresis A diagram, illustrating a mineralocorticoid-responsive cell, is presented As all steroid hormones have in common a cytoplasmic steroidspecific receptor, the importance of these receptors are generally accepted based on evidence from work with either mineralocorticoids, glucocorticoids, or the sex steroids Therefore, mutants of a lymphoma cell-line that lost cellular response to glucocorticoids, are found to be “receptorless,” indicating the crucial role of the receptor The strongest evidence for the role of receptors in the mechanism of action of aldosterone and other steroid hormones is their association with nuclear sites The chapter also discusses the role of RNA and protein synthesis It is concluded that there was synthesis of aldosterone-specific messenger RNA (mRNA) followed by ribosomal RNA (rRNA) The chapter concludes that aldosterone increases Na+ transport because it results in both increased adenosine triphosphate (ATP) synthesis and increased luminal Na+ permeability

Characterization of angiotensin receptors on bovine adrenal fasciculata cells.

Abstract: We have further characterized angiotensin receptors on bovine adrenal fasciculata cells whose presence was previously demonstrated by the intrinsic agonistic activity of angiotensin II (AII), dex-Asp1-AII, angiotensin I (AI), and des-ASp1-AI on steroidogenesis. The specific binding of AII and des-Asp1-AII labeled with 125I to dispersed bovine fasciculata cells was studied. For both peptides, a single class of binding sites accounted for the data with a mean (+/- SEM) Ka value of 0.23 +/- 0.123 X 10(8) liters/mol for AII and 0.68 X 10(8) liters/mol for des-Asp1-AII. The concentration at which unlabeled AII and des-Asp1-AII displaced 50% of the tracers (Kd) was similar to that at which they induced half-maximal stimulation of steroidogenesis (Kact). For AI and des-Asp1-AI, Kd greater than Kact. Analogs of AII or des-Asp1-AII with antagonistic properties upon steroidogenesis competed also with binding of the tracers. Corticotropin (ACTH) did not inhibit binding. Although ACTH stimulated the formation of cyclic AMP, none of the angiotensins with intrinsic activity did so. Calcium, but not potassium, appeared to potentiate the steroidogenic activity of AII. These data suggest that there is a single class of receptors for angiotensins and analogs in zona fasciculata. These receptors show characteristics that differentiate them from ACTH receptors in zona fasciculata or angiotensin receptors in zona glomerulosa cells.

Studies on the mechanism of secretion of corticosteroids by the isolated perfused adrenal of the rat.

Abstract: A technique for the perfusion of the rat adrenal cortex is described. With tissue culture Medium 199 the preparation was responsive in terms of steroid production of both ACTH and K+ ions. Production of corticosterone and 18-hydroxydeoxycorticosterone (18-hydroxy-DOC) was stimulated by ACTH when it was administered at rates between 5 uu.'/min and 5 mu./min. Increasing the K+ ion concentration of the perfusate from 3.6 to 5.4 and 8.9 mmol/l stimulated the production of aldosterone, 18-hydroxycorticosterone and deoxycorticosterone, although not of corticosterone or 18-hydroxy-DOC. This preparation has been used to study further the mechanism of secretion of corticosterone and 18-hydroxy-DOC. Thus, production of these two steroids was measured at different perfusion flows, varying between 0.1 and 0.6ml/min, with different levels of ACTH stimulation. Corticosterone production was significantly (P less than 0.001) increased by increasing flows both under control conditions and with ACTH was administered at constant rates of 50 uu./min or 1 mu./min. Production of 18-hydroxy-DOC was not affected by flow either under control conditions or with 50 uu. ACTH/min. However, when ACTH was administered at 1 mu./min. 18-hydroxy-DOC production was also significantly (P less than 0.001) increased by flow. The results are consistent with those obtained in previous in-vitro studies and have been interpreted as suggesting that the main mechanism of corticosterone secretion is simple diffusion. In contrast, 18-hydroxy-DOC secretion, at least at sub-maximal levels of stimulation, appears to require a more complex process.

The Zonal Origins of the Mineralocorticoid Hormones in the 21-Hydroxylation Deficiency of Congenital Adrenal Hyperplasia*

Abstract: The 0800 h plasma concentrations of the mineralocorticoid hormones, 18-hydroxydeoxycorticosterone (18-OHDOC), deoxycorticosterone (DOC), corticosterone, 18-hydroxycorticosterone (18-OHB), and aldosterone, in six patients with nonsalt-losing congenital adrenal hyperplasia revealed two groupings of these steroids: in one group, DOC, 18-OHB, and aldosterone were significantly elevated (P less than 0.001) at 51.7 +/- 18.0, 70.8 +/- 14.2, and 22.7 +/- 3.0 ng/dl, respectively; in the other group, corticosterone and 18-OHDOC were normal at 363.6 +/- 76.0 and 7.8 +/- 1.1 ng/dl, respectively. No significant increases in response to upright posture were observed in DOC, 18-OHB, or aldosterone. After a 1-h Cortrosyn stimulation test, the already elevated levels of DOC, 18-OHB, and aldosterone showed slight additional increases, but the normal levels of corticosterone and 18-OHDOC changed little within the normal unstimulated range. In these patients certain mineralocorticoid hormone patterns permit the identification of the zonal origins of steroids. The normal and fixed levels of 18-OHDOC and corticosterone, zona fasciculata steroids, are similar to those of cortisol and imply deficiency of formation and of their precursor, zona fasciculata DOC, a 21-hydroxylated steroid. Both the mineralocorticoid and glucocorticoid pathways distal to 21-hydroxylation are impaired in the zona fasciculata. However, the elevated and partially responsive levels of DOC, 18-OHB, and aldosterone imply that there is greater activation of 21-hydroxylation in the zona glomerulosa than in the zona fasciculata, with its normal fixed steroid levels, and that the elevated level of DOC is primarily from this zone.

Morphological correlates of hormone secretion in the rat adrenal cortex and the role of filopodia.

Abstract: Rat adrenals in different states of stimulation were examined by transmission electron microscopy following perfusion fixation using an in situ isolated-circulation technique. In unstimulated glands, intracortical capillaries were constricted and the cells of the cortex were pressed closely together with little development of filopodia or intercellular spaces. Glands fixed during the period of operative stress, or following a 1 hr perfusion with Adrenocorticotropic hormone (ACTH) showed that the radially orientated capillaries of the cortex were massively expanded, and the cells of both the glomerulosa and fasciculata exhibited an extensive development of filopodia on their surfaces. These filopodia extended into enlarged intercellular spaces, where they often entered into complex relationships with filopodia from neighboring cells. The development of filopodia by cells of the adrenal cortex was also observed using scanning electron microscope techniques. In cells either icubated with ACTH in vitro or isolated from adrenals of rats treated with ACTH in vivo, the filopodia were numerous, often branched, and could reach as much as 1 μm in length. In contrast, adrenal cells obtained from animals pretreated with cortisol were smooth surfaced. Other cell characteristics, including mitochondria, smooth endoplasmic reticulum, dense granules, and coated vesicles did not show such dramatic correlations with the state of stimulation. It is considered that the development of filopodia and intercellular space is related to secretory mechanisms in the rat adrenal cortex.

Angiotensin alters 45Ca2+ fluxes in bovine adrenal glomerulosa cells.

Abstract: Angiotensin II stimulated 45Ca2+ release from bovine adrenal glomerulosa cells. It also decreased the influx of 45Ca2+ into glomerulosa cells. The effects were observed within 2 min of hormone addition and were blocked by Saralasin a competitive inhibitor of angiotensin. Des-Phe8-angiotensin II, a biologically inert analog, was inactive in this system. Angiotensin II also inhibited the influx of 133Ba2+ and 54Mn2+, whereas 51Cr6+ and 57Co2+ were unaffected. Alterations in 45Ca2+ fluxes were seen with concentrations of angiotensin that stimulate aldosterone biosynthesis in bovine glomerulosa cell preparations. These results suggest that calcium plays a key role in angiotensin-stimulated aldosteronogenesis.

On the uptake of exogenous catecholamines by adrenal chromaffin cells and nerve endings

Abstract: Light-microscopic autoradiography has revealed characteristic labelling patterns in adrenal medullary cells following the intravenous administration of different catecholamines. The uptake patterns for [3H] dopa, [3H] dopamine, [3H] noradrenaline and [3H] adrenaline have been compared. In all cases A cells were more active than NA cells and cells situated in the zone nearest the cortex demonstrated a markedly higher rate of uptake than central cells. It was concluded that adjacent chromaffin cells with very similar morphology may differ as much as 50 fold in their capacities to incorporate exogenous amines. The adrenergic nature of the innervation of the vessels of the adrenal cortex and capsule in the mouse was confirmed.

Development of the Porcine Fetal Adrenal in Late Gestation

Abstract: Porcine fetal adrenal development at Days 89, 97, 105, and 113 of gestation was investigated. Cortisol secretion by fetal adrenal slices in vitro paralleled fetal plasma cortisol levels previously reported by other investigators, with the greatest increase in both occurring during the last week of gestation. Neither the ACTH dose-response nor the proportional increase in cortisol secretion in response to a maximal dose of ACTH changed from Day 89 to term. At all ages examined, homologous fetal pituitary homogenate had the same effect on cortisol production as a maximal dose of ACTH. Adrenal cortex ultrastructure appeared well developed from Day 89 on. Adrenal weight increased faster than fetal weight, especially between Days 105 and 113. This increase was primarily due to hyperplasia in the adrenal cortex zona fasciculata, although some hypertrophy occurred as well. The increase in cortisol secretion in vitro between Days 89 and 105 could be completely accounted for by adrenal cortex growth. From Days 89 to 105, the cortisol :corticosterone ratio as determined by high pressure liquid chromatography (HPLC) was 1.1 ± 0.3, but increased (P>0.05) to 4.8 ± 0.5 by Day 113. It appears, therefore, that the major adrenal changes contributing to increased cortisol production are 1) mitotic activity in the zona fa.sciculata which increases as term approaches, and 2) increased secretion of cortisol in proportion to other steroids in the last week of gestation.

Role of prostaglandins in the control of the function of adrenal glomerulosa cells.

Abstract: The role of prostaglandins in the control of aldosterone production was studied in isolated rat glomerulosa cells. Exogenous prostaglandin E2 in concentrations above 10(-9) mol/l increased the production rate of aldosterone; this effect was attenuated by the competitive antagonist, 7-oxa-13-prostynoic acid. Prostaglandin F2 alpha (10(-9)--10(-5) mol/l) failed to influence the production rate of aldosterone. The aldosterone-stimulating effect of the prostaglandin precursor, arachidonic acid (5 x 10(-4) mol/l), could not be blocked by inhibitors of prostaglandin synthesis. Basal production rate of aldosterone was not significantly influenced by non-steroidal anti-inflammatory drugs. Glomerulosa cells were stimulated by angiotensin II; this effect was not potentiated by arachidonic acid and was reduced only slightly by indomethacin. The cells were also stimulated by corticotrophin and potassium ions. The effect of these substances was not potentiated by arachidonic acid and was not inhibited by non-steroidal anti-inflammatory drugs. These results do not confirm the presumption that intra-adrenal prostaglandins play an essential role in the control of aldosterone secretion. Some effects of arachidonic acid and its antagonist, eicosatetraynoic acid, on aldosterone production are considered to be independent of changes in prostaglandin synthesis.

Chemical suppression of steroidogenesis.

Abstract: A large number of chemicals are known to interfere with steroidogenesis in the adrenal cortex and other tissues. Many xenobiotics inhibit steroid hormone production as a result of interactions with...

The Control of Steroidogenesis by Human Fetal Adrenal Cells in Tissue Culture. II. Comparison of Morphology and Steroid Production in Cells of the Fetal and Definitive Zones

Abstract: Preparations of dispersed human fetal adrenal cells from the inner third of the gland and from the subcapsular area were maintained in culture, and their ultrastructure and steroid production were studied. The former type of preparation contained only fetal zone cells, while the latter contained definitive zone cells together with varying numbers of fetal zone cells. Both types could be cultured with equal ease, but during short term culture, fetal and definitive zone cells became morphologically indistinguishable. The patterns of steroid production and, in particular, the relative production of delta 4,3-ketosteroids and delta 5,3 beta-hydroxysteroids were similar in both preparations, as were their dose-response relationships during incubation with alpha ACTH-(1-24). Although considerable variability in total steroid production was observed between cells from different adrenal glands, in no specimen was any evidence for functional zonation of the fetal adrenal cortex observed in vitro. The results suggest that the apparently unique histological appearance and function of the fetal adrenal cortex may only reflect intense stimulation by ACTH secondary to the combined influences of a rapid cortisol MCR and of some inhibitor of fetal adrenal 3 beta-hydroxysteroid dehydrogenase activity.