Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

Carter, Anthony Michael; Petersen, Yvette M.; Towstoless, M; Andreasen, Ditte; Jensen, Boye L.

doi:10.1071/rd01046

Cited by 12 publications

(16 citation statements)

References 27 publications

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“…Considering the above, it is surprising that there are two reports that ACTH-(1-24) infusions in fetal sheep do not change ACTH-R mRNA levels (3,25). This may be due to changes in mRNA levels below the assay detection level (25) or doses of ACTH below the threshold for producing an effect on receptor expression.…”

Section: Discussionmentioning

confidence: 82%

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Valego¹,

Su²,

Carey³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At approximately 138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 +/- 1.2 vs. 47.3 +/- 11.1 ng.ml(-1).2 h(-1)) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.

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Section: Discussionmentioning

confidence: 82%

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Valego¹,

Su²,

Carey³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Signals from ACTH are transduced via activation of ACTHR. Previous studies have shown that in sheep, ACTH does not increase fetal adrenal ACTHR mRNA levels 36,37 ; however, other authors have demonstrated a progressive increase in ACTHR mRNA in mid-to late gestation ovine fetal adrenals. 25 This has been confirmed by a more recent publication using different methods of analysis and different doses of ACTH, which also showed a linear relationship between fetal plasma ACTH concentration and receptor mRNA levels, 26 indicating the importance of using more sensitive techniques.…”

Section: Discussionmentioning

confidence: 92%

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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“…Total RNA from sheep adrenal gland (1 μ g) was used as a template for reverse transcription using protocols exactly as described (Carter et al. 2002).…”

Section: Isolation Of Rna From Sheep Organs and Reverse Transcriptionmentioning

confidence: 99%

“…PCR was performed exactly as described (Carter et al. 2002) for 35 cycles consisting of denaturation for 30 s, annealing (45 s at 56 °C), and primer extension (45 s at 72 °C).…”

Section: Isolation Of Rna From Sheep Organs and Reverse Transcriptionmentioning

confidence: 99%

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Adrenomedullin expression during hypoxia in fetal sheep

Jensen

Carter

Skøtt

et al. 2005

Acta Physiologica Scandinavica

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Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

Cited by 12 publications

References 27 publications

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

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

Adrenomedullin expression during hypoxia in fetal sheep

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