Secretion of adrenal zona glomerulosa cells in rats exposed to low doses of dichlorodiphenyltrichloroethane during prenatal and postnatal development

ABSTRACT The actions of forskolin have been investigated to determine to what extent its effects on steroidogenesis in rat adrenal preparations are dependent on activation of adenylate cyclase. In zona glomerulosa preparations, stimulation of both aldosterone and corticosterone production was obtained at concentrations of forskolin between 1 and 10 μmol/l. The effects of 10 μmol forskolin/l were additive with those of low doses (1 pmol/l) of corticotrophin (ACTH), but not with those of high doses (1 nmol/l) of ACTH. In contrast, in zona fasciculata/reticularis cells, doses of forskolin up to 10 μmol/l produced no significant stimulation of corticosterone production either alone or in the presence of ACTH (1 pmol/l and 1 nmol/l). The response to 1 nmol ACTH/l was attenuated in the presence of forskolin (10 μmol/l) in both zona glomerulosa and zona fasciculata/reticularis cell preparations. Cyclic AMP production increased progressively with dose up to 100 μmol forskolin/l in zona glomerulosa cells, whereas corticosterone production was maximal between 10 and 30 μmol forskolin/l and decreased at 100 μmol forskolin/l. In zona fasciculata/reticularis cells, cyclic AMP production was also increased by forskolin (1 and 10 μmol/l). The stimulation of zona glomerulosa steroido-genesis by forskolin (1–10 μmol/l) and ACTH (1–100 pmol/l) were both reduced by the adenylate cyclase inhibitor, N6-phenylisopropyladenosine (100 μmol/l). The calcium channel inhibitor, nifedipine, only reduced the steroidogenic response to forskolin (3 μmol/l) at doses of 300 μmol/l whereas the response to 8·4 mmol K+/l was inhibited at 10 μmol nifedipine/1. Although there is some dissociation between the effects of forskolin on cyclic AMP and steroidogenesis, the results are generally consistent with the view that the effects of forskolin in rat zona glomerulosa cells are mainly dependent on activation of adenylate cyclase. This contrasts with the effects of forskolin in bovine fasciculata cells which are reported to be mediated by activation of voltage-regulated calcium channels. Journal of Endocrinology (1991) 129, 391–397

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The properties of adrenal zona glomerulosa cells after purification by gravitational sedimentation

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1974.0025 ◽

1974 ◽

Vol 185 (1081) ◽

pp. 375-407 ◽

Cited By ~ 39

Keyword(s):

Angiotensin Ii ◽

Cyclic Amp ◽

Microscopic Examination ◽

Zona Glomerulosa ◽

Maximal Response ◽

Zona Fasciculata ◽

Gravitational Sedimentation ◽

Rat Adrenals ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

The densities of latex spheres and biological cells can be reliably determined from their sedimentation rate in an albumin gradient under unit gravitational force. The densities of zona glomerulosa and fasciculata cells of rat adrenals were found to be 1.072 ± 0.004 and 1.040 ± 0.001 respectively. Purified zona glomerulosa cells of rat adrenals can be prepared by gravitational sedimentation of dispersed cells from capsule strippings of the gland, which originally contain 3 to10% zona fasciculata contamination. Electron and phase microscopic examination of the sedimented glomerulosa cells and their steroidogenic response to ACTH and cyclic AMP indicate that they are reasonably free of contamination from zona fasciculata cells. Electron microscopic examination of the purified glomerulosa cells indicates that most of them are reasonably normal in structure. Their basal production of corticosterone is decreased after sedimentation. However, their maximal response of corticosterone output to serotonin and potassium and their response to all potassium concentrations is not significantly altered, indicating normal function for the cells producing steroids. Their maximal responses to ACTH, valine angiotensin II and cyclic AMP are decreased, but, at the doses used, steroidogenesis by the zona fasciculata contamination in the unfractionated preparation would be stimulated by these substances. Purified zona glomerulosa cells have about the same maximal response of corticosterone output (about twofold) to potassium, valine and isoleucine angiotensin II, serotonin and ACTH. The maximal response of the purified zona glomerulosa cells to cyclic AMP is similar to that elicited by valine and isoleucine angiotensin II, potassium, serotonin or ACTH. This indicates that if these stimuli act by increasing cyclic AMP output, then the maximal response of corticosterone output (about twofold) is defined by the limited response of the biosynthetic pathways to cyclic AMP.

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