Katalin Sz. Szalay

Effect of beta-endorphin on the steroid production of isolated zona glomerulosa and zona fasciculata cells.

Abstract Small doses of β-endorphin (10−11−10−5M) decrease corticosterone production of zona fasciculata cells but fail to influence steroid production of zona glomerulosa cells. 10−4M β-endorphin increases corticosterone production of both zones. The stimulating effect of ACTH on zona fasciculata corticosterone- and zona glomerulosa aldosterone production was decreased by β-endorphin (10−9−10−7M). Conclusion: β-endorphin might modulate both basal and ACTH stimulated corticosterone secretion.

Adenovirus infection dramatically augments lipopolysaccharide-induced TNF production and sensitizes to lethal shock

We observed a remarkable synergism of adenoviruses and LPS in triggering the production of TNF in intact animals. We found that in mice pre-exposed to adenoviruses, LPS injections generated extremely high levels of TNF with altered kinetics. The elevated TNF synthesis stemmed mostly from posttranscriptional up-regulation of TNF production, although transcription of the TNF gene was also induced. Adenoviruses and LPS exhibited a significant but less dramatic synergism in the induction of IL-6, IFN-γ, and NO. Only marginal changes were detected in the synthesis of a panel of other cytokines. Different serotypes of the virus showed practically identical effects. As deletion mutants lacking indispensable viral genes or UV inactivated virions exhibited similar activities as the infectious, wild-type virus, it seems unlikely that the viral genome plays any significant role in the phenomenon. Published data indicate that other viruses also show some kind of synergism with LPS, although by different cellular mechanisms. T cells and their IFN-γ production—crucial in the synergism of influenza viruses and LPS—were dispensable in our experiments. We suggest that the phenomenon is probably a general one: an overlap between different molecular mechanisms detecting bacterial and viral pathogens and inducing mediators of nonspecific cell-mediated host defense. The synergism of viruses and LPS (bacteria) could be a concern in medical practice as well as in gene therapy experiments with high doses of recombinant adenoviruses.

Effect of alpha-MSH on the corticosteroid production of isolated zona glomerulosa and zona fasciculata cells

Abstract α-MSH (10 −9 − 6×10 −7 M) potentiates the effect of ACTH (10 −11 − 5×10 −9 M) on adrenocortical steroidogenesis decreassng ED 50 of ACTH from 220 to 183 pg/ml on zona fasciculata corticosterone-, and from 739 to 437 pg/ml on zona glomerulosa aldosterone production. α-MSH alone increases aldosterone production of zona glomerulosa cells in doses (10 −9 − 6×10 −7 M) that do not stimulate zona fasciculata corticosterone production. The response of zona glomerulosa aldosterone production to α-MSH can be characterized by a bi-phase dose-response curve.

Correlation of lipid droplet content and steroidogenic capacity in zona glomerulosa and fasciculata cells from lipoprotein-deficient rats

Lipoprotein deficiency was maintained for 48 h by applying 4-aminopyrazolo(3,4-d)pyrimidine in male albino rats and the effect on the structure and function of isolated adrenocortical cells was investigated. Neither the morphology nor the steroidogenic response of zona glomerulosa cells changed; however, in the zona fasciculata cells a marked reduction in the quantity of lipid droplets was associated with a decreased steroidogenic response to ACTH. The results indicate that despite lipoprotein deficiency, zona glomerulosa cells contain a reserve of intracellular cholesterol, thus retaining their responsiveness to stimulation. The fact that the lipoprotein deficiency does not affect lipid droplets located in the glomerulosa cells and in the fasciculata cells in a similar manner is probably due to the differences in their physical state and chemical composition.

Effects of pro-opiomelanocortin peptides on adrenocortical steroidogenesis

Whilst studying the effects of pro-opiomelanocortin (POMC) peptides on adrenocortical steroidogenesis we showed that alpha-melanocyte-stimulating hormone (alpha-MSH) has a specific glomerulotropic effect and potentiates both the mineralocorticotropic and glucocorticotropic effects of ACTH. The fragments ACTH-(4-10) and ACTH-(11-13) are responsible for the glomerulotropic effect of alpha-MSH. beta-Endorphin enhances, inhibits or has no effect on corticosteroidogenesis, depending on the dose and on the functional state of the adrenocortical cells (saturation of the receptors). beta-Endorphin antagonizes the effect of alpha-MSH on aldosterone production. It is suggested that the modulatory effects of POMC peptides on adrenocortical steroidogenesis may be of physiological significance.

Interactions between ouabain, atrial natriuretic peptide, angiotensin-II and potassium: Effects on rat zona glomerulosa aldosterone production

The effects of ouabain, atrial natriuretic peptide, angiotensin-II and potassium on aldosterone production by collagenase dispersed rat zona glomerulosa cells were studied. A-II and 10(-4) M ouabain-induced increases in aldosterone production was inhibited by 10(-9) M ANP at all potassium concentrations examined. 10(-4) M ouabain inhibited the A-II induced increase in aldosterone production at all potassium concentrations. The degree of this inhibition was smaller at higher potassium levels. Ouabain enhanced the inhibitory effect of ANP on A-II-induced aldosterone synthesis at all potassium concentrations. Interactions between A-II, ANP, ouabain and potassium may be of physiological significance in the regulation of aldosterone secretion.

Effects of ACTH-(11-24) on the corticosteroid production of isolated adrenocortical cells.

The steroidogenic action of ACTH-(11-24) was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(11-24) stimulated the corticosterone production of zona fasciculata cells and the aldosterone production of zona glomerulosa cells; in addition, it potentiated the effects of ACTH-(1-39) on both cell systems. It is suggested that the ACTH molecule contains more active sites for steroidogenesis than usually acknowledged, as has been found for lipolysis and behavior.

Morphological evidence of lysosomal uptake of high-density lipoproteins by rat adrenocortical cells in vitro

The high-density lipoprotein (HDL) pathway in rat adrenocortical cells was studied at the electron microscopic level in vitro via colloidal gold labelling. Steroid hormone assays were performed to confirm that the cells remained intact, viable, responsive to ACTH under the applied conditions, and to reveal the steroidogenic effect of HDL. The gold-labelled HDL particles (HDL-Au) were observed on the surface of the parenchymal cells, often attached to the membranes of the microvilli, but rarely in coated pits and coated vesicles. HDL-Au was accumulated by non-coated vesicles, multivesicular bodies and lysosomes. The lysosomes were identified by means of a non-specific esterase reaction. It is concluded that HDL particles are internalized by both zona glomerulosa and zona fasciculata cells. HDL is required for the enhanced functional activity of these cells in long-term incubation, and the lysosomes are involved in the process.

Interrelationship between corticosteroid production and fine structure in the fetal adrenal cortex.

Abstract The cat fetal adrenal is capable of corticosteroid production from an early stage of ontogenesis (crown-rump length: 2–3 cm) and reacts to ACTH by corticosteroid production. Its hormone-producing ability and responsiveness to ACTH operate before the fine structure characterizing the adult zona fasciculata cells is recognizable. In tissue culture of human fetal adrenal, corticosteroids are produced in response to ACTH even if the fine structure of the endoplasmic reticulum and mitochondria, on which corticosteroid production is currently believed to depend, shows marked deviation from the histological picture characterizing the zona fasciculata cells.

Interaction of ACTH, β‐endorphin and α‐melanocyte stimulating hormone in relation to the corticosteroid production of isolated rat adrenocortical zona fasciculata and zona glomerulosa cells

The combined effects of ACTH, β‐endorphin (β‐EP) and α‐MSH were studied on the corticosteroidogenesis or isolated rat adrenocortical zona fasciculata and zona glomerulosa cells. β‐EP potentiated the effects of ACTH and α‐MSH on the zona fasciculata corticosterone production but inhibited those on the zona glomerulosa aldosterone production. β‐EP did not affect the combined action of 4×10−11 M ACTH and 5×10−9 M α‐MSH on the zona fasciculata or the zona glomerulosa cells, but it inhibited the stimulatory action of the combination of 1.6×10−10 M ACTH and 10−9 M α‐MSH on the zona glomerulosa aldosterone production. An interaction of ACTH, β‐EP and α‐MSH in relation to the zona fasciculata and zona glomerulosa corticosteroid production was found.