Developmental Changes in Adrenocorticotrophin (ACTH)-Induced Expression of ACTH Receptor and Steroid Acute Regulatory Protein mRNA in Ovine Fetal Adrenal Cells

Su, Yixin; Carey, Luke C.; Valego, Nancy K.; Rose, James C.

doi:10.1016/j.jsgi.2005.05.001

Cited by 6 publications

(10 citation statements)

References 29 publications

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“…In agreement with previous studies (Le Roy et al 2000; Rehman et al 2007; Carey et al 2006; Su et al 2005; Johnston et al 2007; Mountjoy et al 1994), we found that the ACTH receptor-MC2R was significantly stimulated by ACTH incubation (12-fold). We also noticed a significant increase in MRAP mRNA level.…”

Section: Discussionsupporting

confidence: 93%

“…The acute response is mediated by the activity of the StAR protein, which leads to mobilization of cholesterol from cellular stores to the inner mitochondrial membrane where cholesterol side-chain cleavage (CYP11A1) is located (Fleury et al 1998; Ariyoshi et al 1998; Fleury et al 1996; Clark & Combs 1999; Lehoux et al 2003). Studies in fetal and adult adrenals across several species have shown that the chronic response of ACTH includes the activation of genes encoding the steroidogenic enzymes, HSD3B2, CYP21, CYP17, CYP11B1 (Neri et al 1991; Phillips et al 1996; Simmonds et al 2001; Bassett et al 2004; Schimmer et al 2006; Carey et al 2006; Coulter & Jaffe 1998; Di Blasio et al 1990; Galtier et al 1996; Lebrethon et al 1994; Mason et al 1993; Su et al 2005; Su & Rose 2008; Tangalakis et al 1990; Zhang et al 1999). These gene targets were confirmed in the current study in AA and FA cells using microarray analysis.…”

Section: Discussionmentioning

confidence: 99%

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ACTH is a potent regulator of gene expression in human adrenal cells

Xing

Parker

Edwards

et al. 2010

Journal of Molecular Endocrinology

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The adrenal glands are the primary source of minerocorticoids, glucocorticoids and the so-called adrenal androgens. Under physiological conditions cortisol and adrenal androgen synthesis are controlled primarily by adrenocorticotrophic hormone (ACTH). Although it has been established that ACTH can stimulate steroidogenesis, the effects of ACTH on overall gene expression in human adrenal cells have not been established. In this study, we defined the effects of chronic ACTH treatment on global gene expression in primary cultures of both adult adrenal (AA) and fetal adrenal (FA) cells. Microarray analysis indicated that 48 h of ACTH treatment caused 30 AA genes and 84 AA genes to increase by greater than 4-fold, with 20 genes common in both cell cultures. Among these genes were six encoding enzymes involved in steroid biosynthesis, the ACTH receptor and its accessory protein, MRAP (ACTH receptor accessory protein). These data provide a group of ACTH-regulated genes including many that have not previously been studied with regard to adrenal function. These genes represent candidates for regulation of adrenal differentiation and steroid hormone biosynthesis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

ACTH is a potent regulator of gene expression in human adrenal cells

Xing

Parker

Edwards

et al. 2010

Journal of Molecular Endocrinology

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show abstract

“…(c) Fetal adrenal gland. Sheep fetal adrenal gland explants responded to ACTH by increasing cortisol production as reported by others (Wintour et al 1975;Su et al 2005) (Fig. 3A).…”

Section: Detection Of a Functional Melatonin Receptor In Sheep Fetal supporting

confidence: 77%

“…Lastly, the sheep fetal adrenal gland shows a complex temporal pattern of longitudinal changes in function, being very responsive to ACTH early in gestation, then loosing this responsivity at mid‐gestation to become very sensitive at term (Wintour et al 1975; Llanos et al 1979; Su et al 2005), thus producing the major increase in cortisol during the last days of pregnancy, responsible for maturation of fetal organs, such as lungs in human and other species (Liggins, 1976) and induction of parturition in sheep (Liggins et al 1973). In the present study, the fetal adrenal gland explants showed the robust response to ACTH described by others after 130 days of gestation (Wintour et al 1975; Su et al 2005). Melatonin inhibited ACTH‐stimulated cortisol production, an effect that was completely reversed by luzindole.…”

Section: Discussionmentioning

confidence: 99%

Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland

Torres-Farfán

Valenzuela

Mondaca

et al. 2008

The Journal of Physiology

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Although the fetal pineal gland does not secrete melatonin, the fetus is exposed to melatonin of maternal origin. In the non-human primate fetus, melatonin acts as a trophic hormone for the adrenal gland, stimulating growth while restraining cortisol production. This latter physiological activity led us to hypothesize that melatonin may influence some fetal functions critical for neonatal adaptation to extrauterine life. To test this hypothesis we explored (i) the presence of G-protein-coupled melatonin binding sites and (ii) the direct modulatory effects of melatonin on noradrenaline (norepinephrine)-induced middle cerebral artery (MCA) contraction, brown adipose tissue (BAT) lypolysis and ACTH-induced adrenal cortisol production in fetal sheep. We found that melatonin directly inhibits the response to noradrenaline in the MCA and BAT, and also inhibits the response to ACTH in the adrenal gland. Melatonin inhibition was reversed by the melatonin antagonist luzindole only in the fetal adrenal. MCA, BAT and adrenal tissue displayed specific high-affinity melatonin binding sites coupled to G-protein (K d values: MCA 64 ± 1 pm, BAT 98.44 ± 2.12 pm and adrenal 4.123 ± 3.22 pm). Melatonin binding was displaced by luzindole only in the adrenal gland, supporting the idea that action in the MCA and BAT is mediated by different melatonin receptors. These direct inhibitory responses to melatonin support a role for melatonin in fetal physiology, which we propose prevents major contraction of cerebral vessels, restrains cortisol release and restricts BAT lypolysis during fetal life.

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“…24 Studies in sheep have shown that ACTHR levels increase progressively in fetal life 25,26 and that ACTH can induce ovine fetal adrenal cell ACTHR expression. 27 Previous human studies have demonstrated that ACTH can induce expression of its own receptor in both HFA DZ/TZ and FZ cells and in adrenocortical tumor-derived NCI H295 cells. [28][29][30] Angiotensin II is the only other peptide hormone that has been found to upregulate ACTHR mRNA in midgestation HFA cells.…”

mentioning

confidence: 99%

The Regulation of Adrenocorticotrophic Hormone Receptor by Corticotropin-Releasing Hormone in Human Fetal Adrenal Definitive/Transitional Zone Cells

et al. 2007

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As gestation progresses, human fetal adrenals (HFA) initiate the production of cortisol, which increases placental corticotropin-releasing hormone (CRH) biosynthesis. While adrenocorticotrophic hormone (ACTH) is important for the onset of cortisol production, the late gestational surge in cortisol production occurs despite falling ACTH levels in the fetal circulation. The authors determine if CRH directly regulates the expression of the ACTH receptor (ACTHR) in HFA definitive/transitional zone (DZ/TZ) cells. DZ/TZ cells isolated from midgestation HFA were cultured before treatment with 0.01 nM to 100 nM CRH or ACTH. Cortisol was measured by radioimmunoassay. Real-time reverse-transcriptase polymerase chain reaction was used to measure ACTHR mRNA. Whole-cell ACTH binding studies were performed using I(125) (Tyr-23) ACTH. CRH produced a dose-dependent rise in cortisol production and caused a time-dependent increase in ACTHR mRNA levels between 12 and 24 hours. As little as 0.1 nM CRH induced ACTHR transcript by 12-fold at 24 hours. Together with ACTH 0.01 nM, 0.03 or 0.1 nM CRH increased ACTHR expression more than ACTH alone. Binding assays demonstrated a 3.5-fold increase in ACTHR protein at 48 hours with combined CRH and ACTH treatment. Physiologic levels of CRH seen in the late-gestation fetus stimulate DZ/TZ ACTHR expression. Since placental CRH production increases strikingly near the end of gestation, the authors suggest that CRH-induced ACTH receptor expression may increase TZ responsiveness to circulating ACTH and contribute to the late gestational rise in cortisol secretion by the HFA, participating in an endocrine cascade that is involved in fetal organ maturation and potentially in the timing of human parturition.

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Developmental Changes in Adrenocorticotrophin (ACTH)-Induced Expression of ACTH Receptor and Steroid Acute Regulatory Protein mRNA in Ovine Fetal Adrenal Cells

Abstract: The data suggest that ACTH-R and StAR are indeed key mediators of fetal adrenocortical responsiveness, and that ACTH is able to up-regulate responsiveness, and hence cortisol production, by increasing their expression.

Cited by 6 publications

References 29 publications

ACTH is a potent regulator of gene expression in human adrenal cells

ACTH is a potent regulator of gene expression in human adrenal cells

Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland

The Regulation of Adrenocorticotrophic Hormone Receptor by Corticotropin-Releasing Hormone in Human Fetal Adrenal Definitive/Transitional Zone Cells

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