Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture

Branchaud, Charlotte L.; Goodyer, Cynthia G.; Hall, Calvin S.; Arató, J; SiliBan, R.E.; Giroud, C. J. P.

doi:10.1016/0039-128x(78)90037-5

Cited by 55 publications

(18 citation statements)

References 8 publications

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“…In definitive zone cultures, ACTH increased production of both steroids with a ratio of 1 : 1 to 0.8: 1. These results with definitive zone cultures agree with those of Branchaud et al [55], who reported that definitive zone cells, like the adult cortex, produce significant amounts of Assteroids. After 15 h treatment the rate of cortisol production in both cultures increased, suggesting a change in the steroidogenic pathway.…”

Section: It Is Uncertain How the Fetal Zone Of The Primate Adrenal Cosupporting

confidence: 93%

Hormonal regulation of the adrenocortical cell

1980

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Monolayer cultures of bovine and human adrenocortical cells have been used to study regulation of growth and function. Homogeneous bovine adrenocortical cells exhibit a finite life span of approximately 60 generations in culture. Full maintenance of differentiated function (steroid hormone synthesis) requires an inducer such as ACTH and antioxidizing conditions. Full induction of differentiated function occurs only when cellular hypertrophy is stimulated by growth factors such as fibroblast growth factor and serum. ACTH and other agents that increase cellular cAMP inhibit replication but do not block growth factor-induced cellular hypertrophy. ACTH and growth factors together result in a hypertrophied, hyperfunctional cell. Replication ensues only when desensitization to the growth inhibitory effects of ACTH occurs. Cultures of the definitive and fetal zones of the human fetal adrenal cortex synthesize the steroids characteristic of the two zones in vivo. ACTH stimulates production of dehydroepiandrosterone (DHA), the major steroid product of the fetal zone, and of cortisol, the characteristic steroid product of the definitive zone. Prolonged ACTH treatment of fetal zone cultures results in a preferential increase in cortisol production so that the pattern of steroid synthesis becomes that of the definitive zone. The preferential increase in cortisol production by fetal Zone cultures results from induction of 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity, which is limiting in fetal zone cells. ACTH thus causes a phenotypic change in fetal zone cells to that of definitive zone cells. In both bovine and human adrenocortical cells, the principal effect of ACTH is to induce full expression of differentiated function. This occurs only under conditions where growth substances and nutrients permit full amplification.

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Section: It Is Uncertain How the Fetal Zone Of The Primate Adrenal Cosupporting

confidence: 93%

Hormonal regulation of the adrenocortical cell

1980

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“…Interesting results have also been obtained by Reynolds et al (19), who have shown that infants with intrauterine growth retardation had normal cortisol synthesis but reduced 3/?-hydroxy-5-ene production. When cultured fetal adrenal cortex cells are exposed to ACTH, only cortisol production is markedly enhanced; DHA-sulfate production is merely maintained (20). In one of our patients (Sib 2), we did not observe any excretion of 3/?-hydroxy-5-ene steroids during ACTH stimulation.…”

Section: Discussionmentioning

confidence: 48%

Deficient 3β-Hydroxy-5-Ene Steroid Secretion by Newborn Infants

Shackleton

Swift

Savage

et al. 1979

The Journal of Clinical Endocrinology & Metabolism

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Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.

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“…In the same experiment, we found an in crease in pituitary content of des-a-MSH, whereas that of a-MSH was reduced [18]. However, in vitro experiments gave contro versial data about the ability of these hor mones to stimulating adrenal androgen se cretion [19][20][21], and the identification of the factor responsible for the adrenal sprout in fetal life still remains to be solved.…”

Section: Discussionmentioning

confidence: 80%

Pituitary Changes of Desacetyl-α-Melanocyte-Stimulating Hormone throughout Development

Facchinetti¹,

Storchi²,

Furani³

et al. 1988

Neonatology

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Adrenocorticotropin (ACTH), α-melanocyte-stimulating hormone (α-MSH) and desacetyl-α-MSH (des-α-MSH) concentrations were evaluated in 4 embryos and 18 fetal pituitaries collected after spontaneous (n = 9) and prostaglandin-induced abortion (n = 9) at 13–25 weeks of gestation. The peptides were measured by radioimmunoassays after a high-performance liquid chromatographic separation of the homogenates. In both embryonic and fetal pituitaries, des-α-MSH concentrations were 2–4 times higher than those of α-MSH and 1- to 50-fold increased in comparison to those of ACTH. Either melanotropin showed the highest pituitary content in the first part of the second trimester, while the ACTH content remained constant. In the oldest fetuses (over 20th week), the pituitaries collected after prostaglandin-induced abortion showed markedly increased values of both des-α-MSH and α-MSH in comparison to samples collected after spontaneous abortion. In conclusion, des-α-MSH, the typical melanotropic hormone of fetal pituitary, undergoes important changes during development. Des-α-MSH seems to be the end product of proopiomelanocortin cleavage and its pituitary content increases in concomitance with the fetal adrenal sprout. Moreover, these data indicate that the intermediate pituitary lobe could be activated by the stress of labor after the 20th week of pregnancy.

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Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture

Cited by 55 publications

References 8 publications

Hormonal regulation of the adrenocortical cell

Hormonal regulation of the adrenocortical cell

Deficient 3β-Hydroxy-5-Ene Steroid Secretion by Newborn Infants

Pituitary Changes of Desacetyl-α-Melanocyte-Stimulating Hormone throughout Development

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