Hormonal Control of Adrenocortical Cell Proliferation

Hornsby, Peter J.; Gill, Gordon N.

doi:10.1172/jci108782

Cited by 122 publications

(31 citation statements)

References 38 publications

(38 reference statements)

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“…Moreover, the addition ofTGF-P did not modify the mitogenic response to FGF. In similar experiments with ACTH, well known for its anti-mitotic activity in vitro (7,15), there were also no interactions with TGF-P (Table 1): incubations with ACTH significantly reduced cell growth; addition of TGF-,B at 100 pg/ml had no effect on the growth inhibiting response to ACTH.…”

Section: Resultsmentioning

confidence: 72%

Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Hotta¹,

Baird²

1986

Proc. Natl. Acad. Sci. U.S.A.

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Transforming growth factor type f 8) suppresses basal as well as corticotropin (ACTH)-stimulated steroid formation by bovine adrenocortical cells in culture. The effect is dose dependent and is not accompanied by any change in adrenocortical cell growth. The minimum effective dose of TGF-.3 is 4 x 10-13 M (10 pg/ml), and maximal inhibition is observed at a concentration of 4 x 10-11 M (1 ng/ml). A 16-to 20-hr incubation with TGF-,B is required to decrease steroidogenesis, and 12-18 hr are required before cells treated with TGF-(3 recover complete responsiveness to corticotropin. Increases in cAMP mediated by corticotropin, forskolin, and isobutylmethylxanthine are not modified by the addition of TGF-(3; thus adenylate cyclase activity is unaffected by TGF-f3.Although TGF-f3 inhibits the formation of all of the A4-steroids measured (including cortisol, corticosterone, aldosterone, and androstenedione), its effect can be completely reversed by the addition of 25-hydroxycholesterol, pregnenolone, or progesterone to the cells. In contrast, the addition of low density lipoprotein has no effect suggesting that TGF-fJ targets the conversion of cholesterol precursors to cholesterol. The results demonstrate a highly potent effect of TGF-,B on the differentiated function of the adrenocortical cell. The inhibition of steroidogenesis can be dissociated from any effect on cell proliferation, and it occurs distal to the formation of cAMP but proximal to the formation of cholesterol. The results suggest that in the adrenal, TGF-,B or TGF-,B-like proteins may be playing an important role in modifying the differentiated state of the adrenocortical cell.

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Section: Resultsmentioning

confidence: 72%

Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Hotta¹,

Baird²

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Lutropin suppresses mitosis of luteal cells (Gospodarowicz and Gospodarowicz, 1975). Corticotropin has an anti-mitotic effect in adrenocortical cells or in adrenal tumor cells (Ramachandran and Suyama, 1975;Hornsby and Gill, 1977;Weidman and Gill, 1977). These hormones may activate adenylate cyclase activity and stimulate secretion of the specific hormone in their respective target cells.…”

Section: Discussionmentioning

confidence: 99%

Bovine thyrotropin inhibits DNA synthesis inversely with stimulation of cyclic AMP production in cultured porcine thyroid follicles.

et al. 1985

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The effects of bovine thyrotropin (TSH) on DNA synthesis and cyclic AMP production were studied in porcine thyroid follicles using suspension culture. During the early 72 hours incubation, the time-dependent uptake of [3H] thymidine by the follicles was obserbed. In the presence of 10mU/ml TSH, the uptake of [3H] thymidine was significantly depressed at 72hours incubation.TSH inhibition of [3H] thymidine incorporation was related to its concentration and the 50% inhibition was observed by using 1.0mU/ml TSH.Under the same conditions, cyclic AMP production was stimulated by TSH and the stimulation was observed to be related to TSH concentration. In these experiments, the incubation time was 30min.Dibutyryl cyclic AMP, an analogue of cyclic AMP, inhibited the [3H] thymidine uptake at 72hours incubation.From these results, it is suggested that TSH inhibits DNA synthesis, and that the inhibition may be mediated by cyclic AMP that is produced by TSH stimulation.

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“…FGF but not EGF stimulates proliferation of these cells, whereas corticotropin (ACTH) and prostaglandin El (PGE1), which stimulate cyclic AMP formation, inhibit proliferation (8,9). Corticotropin and PGE1 both stimulate steroidogenesis and induce the steroid biosynthetic pathway.…”

mentioning

confidence: 99%

Angiotensin stimulation of bovine adrenocortical cell growth.

Gill¹,

Ill²,

Simonian³

1977

Proc. Natl. Acad. Sci. U.S.A.

107

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Factors controlling proliferation of adrenocortical cells have been studied in Although several purified polypeptides have been reported to stimulate the proliferation of animal cells-in culture, a high degree of cell specificity has not been observed. Fibroblast growth factor (FGF) is mitogenic for fibroblast, adrenocortical, myoblast, smooth muscle, chondrocyte, vascular endothelial, granulosa, and luteal cells, whereas epidermal growth factor (EGF) is mitogenic for fibroblast, corneal epithelial, certain mammary epithelial, and granulosa cells (1). Several pituitary polypeptides long considered trophic for specific target cells in ivo either inhibit DNA synthesis when added directly to target cells in culture or have no effect on growth (2-6). Understanding of the mechanisms controlling organ-specific growth is, therefore, incomplete; interaction of several growth factors and hormones may be involved (7).A recently developed strain of bovine adrenocortical cells in culture has been used to study factors controlling proliferation of the adrenal cortical cell (8). FGF but not EGF stimulates proliferation of these cells, whereas corticotropin (ACTH) and prostaglandin El (PGE1), which stimulate cyclic AMP formation, inhibit proliferation (8, 9). Corticotropin and PGE1 both stimulate steroidogenesis and induce the steroid biosynthetic pathway. The present studies indicate that angiotensin II and III at low concentrations stimulate DNA synthesis as well as steroidogenesis in adrenocortical cells. The growth-stimulatory effect of angiotensin appears specific because several cell types, including cells reported to possess angiotensin II receptors, do not increase DNA synthesis with addition of angiotensin II (Schwarz/Mann) was routinely added to cultures 12 hr after addition of growth stimuli. Twelve hours later, medium was removed and 1 ml of a 1% aqueous solution of Triton X-100 was added. The cells were incubated with this solution for 5 min and the entire contents of the plate

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Hormonal Control of Adrenocortical Cell Proliferation

Cited by 122 publications

References 38 publications

Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Bovine thyrotropin inhibits DNA synthesis inversely with stimulation of cyclic AMP production in cultured porcine thyroid follicles.

Angiotensin stimulation of bovine adrenocortical cell growth.

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