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- Author: G. P. Vinson x
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Several aspects of the intracellular mechanisms involved in the steroidogenic response of adrenocortical tissue to stimulation by corticotrophin remain uncertain. As in other systems, the peptide interacts with a specific membrane receptor (see e.g. Buckley & Ramachandran, 1981) and the subsequent activation of adenylate cyclase is one of the classical examples of this system in the literature (Grahame-Smith, Butcher, Ney & Sutherland, 1967), although, because of the incomplete correlation between steroid and cyclic AMP output, other mechanisms for intracellular signal transduction are not necessarily excluded (e.g. Yanagibashi, Kamiya, Lin & Matsuba, 1978; Kojima, Kojima & Rasmussen, 1985; but see also Wong, O'Brien & Schimmer, 1986). Events subsequent to the activation of adenylate cyclase are less clear. Certainly there follows activation of cyclic AMP-dependent protein kinases and, consequently, protein phosphorylation (e.g. Koroscil & Gallant, 1981; Ahrens, Aiyar & Sharma, 1986; Wong et al. 1986) but how this in turn leads to
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SUMMARY
Minced rat adrenal glands were incubated in vitro with [4-14C]progesterone and [16-3H]pregnenolone separately and together for 4 and 6 hr. periods. The yields of corticosterone, 11-deoxycorticosterone, and 18-hydroxy-11-deoxycorticosterone from both precursors, and of progesterone from [16-3H]pregnenolone, were estimated. In three incubations the change of these yields with time was also investigated. The results obtained suggest that in contrast to the human adrenal, and possibly those of other species, there is no distinction between the roles of progesterone and pregnenolone as precursors of corticosteroids in the rat adrenal gland. They suggest also that in the normal rat adrenal gland pregnenolone is transformed as follows:
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SUMMARY
A kinetic study of corticosterone recovered during incubation of rat adrenal tissue with [4-14C]progesterone and [16-3H]pregnenolone shows that both its 3H: 14C ratio and its specific activity change with time throughout incubation. Corticosterone is itself metabolized, and hypotheses based on the rate of production of corticosterone may be therefore deceptive when the amount is measured at a single point in time. Thus disparities between the specific activities of products and intermediates may be expected which alone do not necessarily indicate differences between the biosynthetic pathways involved in production from endogenous precursors and those from added radioactive precursors.
Other experiments suggest that steroids in incubation media, in concentrations comparable with those found in adrenal venous plasma, do not inhibit the continued synthesis of hormones.
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Chester Jones & Henderson (1963), in confirming and extending the work of Groat (1943, 1944), showed that new tissue, presumably adrenocortical in nature, appeared in the ovaries and adnexa of adrenalectomized ground squirrels. In a series of experiments set up to investigate steroid production by this new tissue, interesting results were obtained with the control animals, and these are reported here.
Thirteen-lined ground squirrels (Citellus tridecemlineatus Mitchell) were trapped in Minnesota and sent by air to Sheffield. Eighty-one females that were in anoestrus at the time of the experiments were used. Animals were killed by a blow on the head and the adrenal glands (1491 mg. in total) and ovaries (1269 mg.) were excised, cleaned and minced. No attempt to remove medullary tissue from the adrenal preparations was made. This was considered justifiable in the absence of positive evidence that normal chromaffin cells can effect steroid transformations, although this capacity
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Departments of Zoology, Australian National University, Canberra and St Bartholomew's Medical College, London, EC1M 6BQ
(Received 16 December 1975)
The adrenal cortex of many eutherian mammals is functional at birth and in some species at least may be involved in parturition (e.g. Liggins, Kennedy & Holm, 1967). Marsupials are born after a relatively short gestation and are considerably smaller than eutherian neonates. It has been postulated that the middle of pouch life, when homoiothermy is achieved, is comparable to the time of birth in eutherians (Bentley & Shield, 1962). Homoiothermy in the tammar wallaby, Macropus eugenii, is established between 140 and 170 days of pouch life (Setchell, 1974). Experiments were designed to determine when the adrenal cortex begins to synthesize and secrete steroids.
Male pouch young of the tammar wallaby were bled from the carotid artery, and steroids were extracted with methanol. Adrenals were weighed, chopped and incubated (Vinson, Phillips,
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ABSTRACT
It is now known that in the rat there are two distinct species of cytochrome P45011β/18, namely aldosterone synthase and 11β-hydroxylase. Whereas aldosterone synthase is located exclusively in the zona glomerulosa, the zonal distribution and site of production of 11 β-hydroxylase is not entirely clear. In the present study we examined the zonal expression of 11β-hydroxylase mRNA in adrenals from control rats and animals subjected to ACTH treatment and dietary sodium restriction using a non-isotopic in-situ hybridization technique. The results were compared with those obtained using an inner zone specific antigenic (IZAg) marker to give unequivocal identification of the adrenocortical cell types.
11 β-Hydroxylase mRNA was clearly shown to be expressed in the inner zones of the control rat adrenal cortex, and none was detected in the zona glomerulosa and medulla. The message was more abundant in the outer zona fasciculata. A similar pattern of distribution of 11β-hydroxylase mRNA was observed in adrenals from rats subjected to dietary sodium restriction, although the width of the negatively staining layer of zona glomerulosa was significantly increased. In rats treated with 100 μg ACTH for 1 day, the number of cells expressing 11β-hydroxylase mRNA was increased, especially in the zona reticularis. With continued ACTH treatment, 11β-hydroxylase mRNA was found in the region of the zona glomerulosa, and after 3 and 5 days of ACTH treatment cells expressing 11β-hydroxylase mRNA extended to the connective tissue capsule. At this time there was a significant reduction in the total expression of the message compared with the controls.
These results suggest that the presence of 11β-hydroxylase in the zona glomerulosa cells is not essential for the late pathway for aldosterone biosynthesis from deoxycorticosterone. Like IZAg, the distribution of 11β-hydroxylase mRNA after prolonged ACTH treatment provides further evidence to support the hypothesis that ACTH increases the conversion of zona glomerulosa to zona fasciculata-like cells.
Journal of Endocrinology (1993) 139, 301–306
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Abstract
This study located the particular cell types involved in the synthesis of growth factors in adult female rat adrenal glands. Non-isotopic in situ hybridization was used and the cellular localizations of the mRNAs of basic fibroblast growth factor (bFGF), IGF-I, and transforming growth factor-β1 (TGF-β1) were studied in adrenals from control animals and from those treated with ACTH or subjected to dietary sodium restriction. The adrenal medulla was the richest source of both bFGF and IGF-1 mRNA in both control and experimental rat adrenals. In the cortex, bFGF and IGF-I mRNAs were found mainly in the zona fasciculata in control animals, although some transcription was also detected in the zona reticularis and zona glomerulosa. Both ACTH and sodium restriction activated bFGF and IGF-I gene expression in the zona glomerulosa. Since cellular proliferation and differentiation occur primarily in the outer cortex, the data are consistent with the view that bFGF and IGF-I act as an autocrine/paracrine mitogen and differentiation regulator respectively in the rat adrenal cortex.
Very small amounts of TGF-β1 mRNA were detected, predominantly in the zona fasciculata of control rats. There were no observable differences in amounts and localization of TGF-β1 mRNA between the adrenals of control rats and those treated with ACTH for 1 day. TGF-β1 mRNA was very weak or undetectable in the adrenals from rats treated with ACTH for three and five days or from sodium-restricted rats. Although TGF-β1 immunoreactive protein has been shown to be present in the zonae fasciculata and reticularis and to modulate negatively the steroidogenic activities in the adrenal cortex of other species, its gene is not actively expressed in rat adrenals.
The present results showed that ACTH administration or dietary sodium restriction, both important adrenal mitogens in vivo, significantly altered the spatial patterns of the distribution of bFGF and IGF-I mRNAs and also increased the amount of bFGF mRNA in the adrenal cortex. This suggests that growth and differentiation of the adrenal cortex are partly mediated by bFGF and IGF-I.
Journal of Endocrinology (1995) 144, 379–387
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When hamster adrenal tissue is incubated in Krebs—Ringer solution, cortisone is the major steroid product both from endogenous precursors and from added [4-14C]progesterone (Whitehouse, Vinson & Janssens, 1966, 1967); added radioactive cortisol is rapidly converted into cortisone by hamster adrenal tissue in vitro although cortisol appears to be the main hormonal steroid of the adrenal venous blood. Whole blood of the hamster shows some capacity to reduce cortisone to cortisol, but this seems insufficient to account for the relatively lower yields of cortisone obtained when adrenal tissue is incubated with [4-14C]progesterone in hamster whole blood. Consequently it may be assumed that the function of the adrenal enzymes is modified by factors in the blood.
The metabolic pathway of progesterone involves the stages: progesterone → (intermediates) → cortisol → cortisone, and hence it is possible that the relative amounts of labelled cortisol and cortisone change throughout the
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SUMMARY
The major steroid products of the rat adrenal gland were studied both in vitro and in vivo. It was found that these methods gave similar results with regard both to the nature of the compounds produced and to their relative proportions. In particular, the status of 11-desoxycorticosterone as a physiologically important adrenal product is discussed, and it is concluded that this compound, as well as aldosterone, may possibly be instrumental in controlling electrolyte flux in the rat.
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SUMMARY
The capacity of the adrenal gland of the mouse to form steroids in vitro, using incubation techniques with [4-14C]progesterone, was investigated. Reasons are given for the identification of two oestrogens, 16-oxooestrone and 17-epioestriol and two adrenocorticosteroids, corticosterone and 20α-hydroxycorticosterone. The presence or absence of the X zone did not appear to influence the relative amounts of oestrogens and adrenocorticosteroids produced. No compounds which could be unequivocally characterized as androgens (C19 steroids) were found.
