Effect of Cortisol Infusion on the Pituitary-Adrenal Axis of the Hypothalamo-Pituitary-Disconnected Fetal Sheep

Antolovich, Giuliana; McMillen, I. C.; Robinson, Peter; Silver, Michael; Young, I. R.; Perry, Ryan

doi:10.1159/000126244

Cited by 13 publications

(5 citation statements)

References 15 publications

(26 reference statements)

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“…On a molar basis, it shows 100% cross-reactivity with ovine ACTH-(1-39), human ACTH-(1-39), and ACTH- (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). It also reacts Ͼ90% with ACTH-(1-24) and Ͻ1% with ACTH- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) or human ACTH- . It does not crossreact with ACTH-(1-10), ACTH-(1-10) amide, ACTH-(4-11), ACTH- (11)(12)(13)(14)(15)(16)(17)(18)(19), ACTH-(11-24), or ACTH-(25-39) fragments of the ACTH-(1-39) peptide.…”

Section: Cell Immunoblottingmentioning

confidence: 99%

The role of hypothalamic input on corticotroph maturation in fetal sheep

Young¹,

Tatter

Valego³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Corticotropin-releasing hormone receptor type 1 (CRH-R1) expression and vasopressin type 1b (V1b) receptor protein decrease in late-gestation fetal sheep. Because hypothalamo-pituitary disconnection (HPD) has been demonstrated to prevent the morphological maturation of corticotrophs, we hypothesized that hypothalamic input is necessary for the maturational changes in CRH-R1 and V1b receptor levels. We measured CRH-R1 and V1b receptor expression in the anterior pituitaries of fetuses at 140 days gestational age (dGA) that underwent HPD or sham surgery at 120 dGA. CRH-R1 mRNA decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. However, CRH-R1 protein levels were elevated in HPD fetuses compared with sham and were not different from 120 dGA values. V1b protein levels decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. We conclude that hypothalamic input to the pituitary is necessary for the decrease in CRH-R1 receptor protein levels in late-gestation fetal sheep. However, hypothalamic input is not necessary for the decrease in V1b receptor expression seen in late gestation.

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Section: Cell Immunoblottingmentioning

confidence: 99%

The role of hypothalamic input on corticotroph maturation in fetal sheep

Young¹,

Tatter

Valego³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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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).…”

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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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“…We have reinvestigated this question using the more sophisticated technique of fetal H P D ( 3 ) in which the disconnection is made above the level of both the anterior hypophyseal arteries and long portal vessels, leaving the blood supply to the median eminence, pars tuberalis and pars distalis undisturbed (7). Previous studies with this preparation have shown that plasma ACTH concentrations in H P D fetuses, measured by radioimmunoassay, exceed those of controls before 135 days of gesta- tion after which intact fetuses exhibit an increase in ACTH (8)(9)(10). Elevated ACTH concentrations are also observed in adult sheep following HPD (11)(12)(13).…”

mentioning

confidence: 99%

Effect of Late Hypothalamo‐Pituitary Disconnection on the Development of the HPA Axis in the Ovine Fetus and the Initiation of Parturition

Deayton

Young

Hollingworth

et al. 1994

J Neuroendocrinology

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The studies of Liggins et a/. (1) in which fetuses stalk-sectioned from day 116 onwards delivered at or near term, suggested that a connection between the fetal hypothalamus and pituitary is not essential for parturition to occur. The objective of this study was to repeat these experiments on the effects of pituitary stalk sections at different gestational a g e s and include information on the plasma concentrations of key fetal hormones. We have used the more sophisticated technique of hypothalamo-pituitary disconnection (HPD) at either of two gestational a g e ranges (123-127 days or 133-135 days). Completeness of the procedure was assessed by demonstrating an attenuated prolactin response to chlorpromazine challenge. Following HPD, gestation was prolonged for at least eight days beyond term (146.2j1.5 days) in 9 of the 10 fetuses operated. Fetal plasma ACTH,_,, concentrations were not different between t h e HPD and control fetuses, increasing in all groups with increasing gestation. Fetal plasma cortisol concentrations increased (P

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Effect of Cortisol Infusion on the Pituitary-Adrenal Axis of the Hypothalamo-Pituitary-Disconnected Fetal Sheep

Cited by 13 publications

References 15 publications

The role of hypothalamic input on corticotroph maturation in fetal sheep

The role of hypothalamic input on corticotroph maturation in fetal sheep

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

Effect of Late Hypothalamo‐Pituitary Disconnection on the Development of the HPA Axis in the Ovine Fetus and the Initiation of Parturition

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