The role of hypothalamic input on corticotroph maturation  in fetal sheep

Young, Sharla F.; Tatter, Stephen B.; Valego, Nancy K.; Figueroa, Jorge; Thompson, Jalonda; Rose, James C.

doi:10.1152/ajpregu.00572.2002

Cited by 9 publications

(7 citation statements)

References 50 publications

(78 reference statements)

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“…We were successful in achieving this, as indicated by the fact that the concentrations attained after infusion (which were stable at ϳ30 ng/ml after the first 6 h) were comparable to concentrations in sham-operated fetuses. These levels are also in accordance with previous reports concerning similarly aged non-HPD fetuses (6,25). We acknowledge that the rapid increase in cortisol concentrations after the initiation of infusion is not overly physiological in terms of mimicking the cortisol surge.…”

Section: Discussionsupporting

confidence: 92%

“…As previously noted, there is also compelling evidence suggesting that the fetal sheep pituitary becomes increasingly responsive to AVP with advancing gestation (9,16), while responsiveness to corticotropin-releasing hormone concurrently declines. This occurs despite the fact that pituitary AVP receptor expression actually decreases in late gestation (25). We suggest that the change in AVP sensitivity is essential for continued ACTH secretion.…”

Section: Discussionmentioning

confidence: 70%

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Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

Carey¹,

Tatter²,

Rose³

2009

American Journal of Physiology-Endocrinology and Metabolism

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Corticotrophs in the fetal sheep become increasingly responsive to arginine vasopressin (AVP) in late gestation. We previously reported that this may be due in part to corresponding increases in signal transduction (inositol 1,4,5-trisphosphate, IP(3)). These ontogenic changes are prevented by hypothalamo-pituitary disconnection (HPD), which also prevents fetal plasma cortisol concentrations from increasing in late gestation. This led us to hypothesize that cortisol is involved in mediating the changes in pituitary responsiveness. HPD was performed on fetal sheep at 120 days gestational age (dGA). Half of the HPD fetuses were infused with cortisol for 3 days beginning at 135-137 dGA (HPD+C). The remaining HPD fetuses and a group of sham-operated control fetuses were infused with saline. Pituitary cells were isolated and cultured. After 48 h, a subset of cells was stimulated with 100 nM AVP for 2 h, and the medium was collected for ACTH analysis. Another subset of cells was stimulated with 100 nM AVP for 30 min, and the formation of IP(3) was determined. Plasma cortisol concentrations increased rapidly within the first 6 h after infusion (5.2 +/- 1.9 to 29.7 +/- 4.9 ng/ml) but did not increase thereafter. Cells from HPD+C and sham-operated fetuses secreted significantly more ACTH than those from HPD fetuses (% increase from control: 33.0 +/- 8.8%, 47.9 +/- 10.6%, and 11.9 +/- 2.4%, respectively). IP(3) formation was significantly increased in cells from HPD+C and sham-operated compared with HPD fetuses (% increase from control: 17.7 +/- 4.4%, 18.9 +/- 4.3%, and 4.6 +/- 1.5%, respectively). These findings support the idea that cortisol plays a role in mediating the increase in pituitary responsiveness to AVP in the late-gestation fetal sheep.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 70%

Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

Carey¹,

Tatter²,

Rose³

2009

American Journal of Physiology-Endocrinology and Metabolism

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“…An intact hypothalamic pituitary connection is essential, as clearly demonstrated by hypothalamic pituitary disconnection (HPD) studies in fetal sheep, in which the major consequences of this disruption are the absence of the cortisol surge (11,34,38,48,53) and delayed parturition (1, 2, 4, 33). Increased adrenal responsiveness also is a critical mediating factor (18,21,41,51).…”

mentioning

confidence: 99%

Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep

Carey¹,

Su²,

Valego³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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-The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness. Hence, we examined effects of ACTH infusion in fetal sheep on mRNA expression of these two mediators of adrenal responsiveness and assessed the functional consequences of this treatment in vitro. Fetuses of ϳ118 and 138 days of gestational age (dGA) were infused with ACTH-(1-24) for 24 h. Controls received saline infusion. Arterial blood was sampled throughout the infusion. Adrenals were isolated and analyzed for ACTH-R and StAR mRNA, or cells were cultured for 48 h. Cells were stimulated with ACTH, and medium was collected for cortisol measurement. Fetal plasma ACTH and cortisol concentrations increased over the infusion period in both groups. ACTH-R mRNA levels were significantly higher in ACTH-infused fetuses in both the 118 and 138 dGA groups. StAR mRNA increased significantly in both the 118 and 138 dGA groups. Adrenal cells from ACTH-infused fetuses were significantly more responsive to ACTH stimulation in terms of cortisol secretion than those from saline-infused controls. These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH-R and StAR mRNA and are coupled to heightened adrenal responsiveness. adrenocorticotropic hormone; ovine fetus IN HUMANS AND MANY MAMMALIAN SPECIES, the late-gestation surge in fetal plasma cortisol levels stimulates final stage development of the lung and other organ systems (7, 22) and indeed, in sheep, initiates birth (19, 32). Parturition occurring before this surge is associated with increased fetal mortality and morbidity, most notably as a consequence of lung immaturity. Whereas the sequence of events leading to cortisol production per se are well understood, the precise mechanisms involved in driving the rise in fetal plasma cortisol in late gestation are yet to be fully explained.It is apparent that important changes take place at each level of the hypothalamic-pituitary adrenal axis, leading to the prepartum increase in fetal plasma cortisol. An intact hypothalamic pituitary connection is essential, as clearly demonstrated by hypothalamic pituitary disconnection (HPD) studies in fetal sheep, in which the major consequences of this disruption are the absence of the cortisol surge (11,34,38,48,53) and delayed parturition (1, 2, 4, 33). Increased adrenal responsiveness also is a critical mediating factor (18,21,41,51). Two important effectors to this end, the adrenocorticotropic hormone receptor (ACTH-R, specifically known as the melanocortin-2 receptor) and steroid acute regulatory protein (StAR), exhibit ontogenic increases in expression that occur in parallel to the cortisol surge (8,17,49)...

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“…Surgeries were performed at ϳ120 days of gestational age (dGA). Polyvinyl catheters previously filled with sterile saline were inserted into the fetal femoral arteries and veins and advanced to the descending aorta and inferior vena cava, and HPD was performed as described by Antolovich et al (1), with slight modifications (72).…”

Section: Methodsmentioning

confidence: 99%

“…Disconnecting the hypothalamus from the pituitary (hypothalamic-pituitary disconnection, HPD) results in retarded HPA axis development and resultant activity. Most notably, following HPD there is no surge in fetal plasma cortisol concentrations in late gestation (2,3,12,72). With this in mind, the present study was designed to examine the importance of endogenous cortisol in regulating the fetal sheep RAS in late gestation, specifically by assessing how blocking the naturally occurring increase in cortisol levels close to term affects plasma and renal renin and prorenin concentrations, and AT1 and AT2 receptor expression in kidney, heart, and lung.…”

mentioning

confidence: 99%

The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep

Chen¹,

Carey²,

Liu³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known. Therefore, we utilized the technique of hypothalamic-pituitary disconnection (HPD), which prevents the cortisol surge from occurring, to investigate the importance of the late-gestation increase in cortisol on the ontogenic changes in RAS activity. HPD of fetal sheep was performed at 120 days of gestational age (dGA), and fetuses were delivered between 135 and 139 dGA. Control fetuses were sham operated. HPD blocked the late-gestation cortisol increase but did not alter renal renin mRNA, renal renin or prorenin protein content, nor plasma renin levels compared with sham operated. However, HPD fetuses had increased ANG II receptor subtype 1 (AT1) mRNA and protein expression in the kidney and lungs. ANG II receptor subtype 2 (AT2) expression was not altered in these tissues at either mRNA or protein level. HPD did not change AT1 or AT2 mRNA in the left ventricle but did result in decreased protein levels for both receptors. These studies demonstrate that blockade of the naturally occurring increase in fetal cortisol concentration in late gestation is associated with tissue-specific alterations in expression of AT1 and AT2 receptors. These changes may impact on fetal tissue maturation and hence have consequences in postnatal life.

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The role of hypothalamic input on corticotroph maturation in fetal sheep

Cited by 9 publications

References 50 publications

Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep

The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep

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