Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

Bruder, Eric D.; Taylor, Jennifer; Kamer, Kimberli J.; Raff, Hershel

doi:10.1152/ajpregu.90400.2008

Cited by 40 publications

(62 citation statements)

References 64 publications

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“…We have previously shown that acute, continuous hypoxia resulted in a pituitary-adrenal response in neonatal rats (4). In the present study, IH elicited a large increase in ACTH and an associated increase in corticosterone in older animals.…”

Section: Discussionsupporting

confidence: 66%

“…In the present study, IH elicited a large increase in ACTH and an associated increase in corticosterone in older animals. These responses represented an adult-type, ACTH-dependent increase in corticosterone in response to stress (4). Interestingly, the corticosterone response to IH in PD2 rats was the greatest in magnitude but was associated with a very small increase in plasma ACTH.…”

Section: Discussionmentioning

confidence: 94%

“…First, it is possible that increased corticosterone production is stimulated by IH-induced sympathetic drive to the adrenal cortex, which is innervated by postganglionic sympathetic neurons (25). This innervation is present and functional in the immature adrenal gland (3,4). Second, the response may be due to increased sensitivity of the adrenal cortex to very small changes in ACTH in the PD2 pups.…”

Section: Discussionmentioning

confidence: 99%

“…All analytic techniques have been published previously (4). Briefly, plasma ACTH and corticosterone were measured by radioimmunoassay (MP Biomedicals, Solon, OH).…”

Section: Methodsmentioning

confidence: 99%

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Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

Chintamaneni

Bruder

Raff

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Chintamaneni K, Bruder ED, Raff H. Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat. Am J Physiol Regul Integr Comp Physiol 304: R782-R789, 2013. First published March 13, 2013 doi:10.1152/ajpregu.00073.2013.-Apnea, the temporary cessation of respiratory airflow, is a common cause of intermittent hypoxia (IH) in premature infants. We hypothesized that IH elicits a stress response and alters glucose homeostasis in the neonatal rat. Rat pups were studied on postnatal day (PD) 2, 8, 10, 12, and 14. Pups were exposed to normoxia (control) or six cycles consisting of 30-s exposures to hypoxia (FIO 2 ϭ 3%) over a 60-min period. Blood samples were obtained at baseline, after the third cycle (ϳ30 min), and after the sixth cycle (ϳ60 min). Tissue samples were collected following the sixth cycle. Plasma ACTH, corticosterone, glucose, and insulin were analyzed at all ages. Hypothalamic, pituitary, and adrenal mRNA expression was evaluated by quantitative PCR in PD2, PD8, and PD12 pups. Exposure to IH elicited significant increases in plasma ACTH and corticosterone at all ages studied. The largest increase in corticosterone occurred in PD2 pups, despite only a very small increase in plasma ACTH. This ACTH-independent increase in corticosterone in PD2 pups was associated with increases in adrenal Ldlr and Star mRNA expression. Additionally, IH caused hyperglycemia and hyperinsulinemia at all ages. We conclude that IH elicits a significant pituitary-adrenal response and significantly alters glucose homeostasis. Furthermore, the quantitative and qualitative characteristics of these responses depend on developmental age.hypothalamic-pituitary-adrenal axis; newborn; anoxia; apnea; adrenal cortex APNEA, the cessation of respiratory airflow, causes hypoxemia and bradycardia in the neonate (27). Apnea is the most common cause of hypoxia in neonates, particularly with prematurity, and is usually due to immature respiratory control systems (20). Incomplete respiratory maturation may involve deficits in neural respiratory control, central and peripheral chemoreceptors, or coordination of the upper airway muscles (20). It has previously been shown that about half of babies born prematurely (30 -31 wk of gestational age) may experience bouts of apnea (27).We have shown that acute, continuous hypoxia in the neonatal rat, a model of cardiopulmonary disease of prematurity, is a metabolic challenge that elicits a stress response from the hypothalamic-pituitary-adrenal (HPA) axis (3). This experimental model also results in bradycardia, alterations in glucose homeostasis, and a dramatic decrease in body temperature (3, 4, 11).The current study used intermittent hypoxia (IH) as an established model of apnea-induced hypoxia (21). IH mimics spontaneous, short duration episodes of hypoxia that occur during apnea in the neonate. A widely used definition of apnea specifies a 15-to 20-s cessation of breathing, a decrease in oxygen saturation to Ͻ80%, and a refractory period ...

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

“…All analytic techniques have been published previously (4). Briefly, plasma ACTH and corticosterone were measured by radioimmunoassay (MP Biomedicals, Solon, OH).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

Chintamaneni

Bruder

Raff

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Studies in rats and pikas and ewes, exposed to altitude mediate reduced oxygen breathing suggested that hypoxic stress increases release of ACTH via cAMP (4,20). Acute hypoxia seems also to result in increased ACTH release and cortisone blood levels in neonatal rats (21). Intermitent hypoxia has been also shown to suppress GH mRNA expression in adenohypophysis and of GH release in rats (22).…”

Section: Figure 1 Immunohistochemical Staining Of Tissue Sections: (mentioning

confidence: 99%

Hypoxia Inducible Factor Expression and Angiogenesis – Analysis in the Pituitary Gland and Patterns of Death

Kouroupi

Sivridis

Papazoglou

et al. 2018

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Abstract. Background The pituitary (hypophysis), a small 0.5-g endocrine gland, is located at the base of the brain, just below the hypothalamus; it is the "master gland" of the neuroendocrine system for it controls the function of other endocrine glands. The pituitary itself is regulated by the hypothalamus that is connected to the pituitary by a thin stalk, the pituitary stalk, which carries a delicate portal venous system. Microscopically, the pituitary is composed of two distinctive parts: the anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis) (1). The anterior lobe is a typical endocrine gland composed of cells that contain hormone-secreting cytoplasmic granules; these, after a conventional H&E staining, characterize the adenohypophyseal cells as acidophils, basophils and chromophobes. By immunohistochemistry, however, the cells are distinguished in somatotrophs (GH cells), prolactin secreting cells (PRL cells), corticotrophs (ACTH cells), thyrotrophs (TSH cells) and gonadotrophs (FSH and LH cells).As to the posterior lobe, this being an extension of the hypothalamus, is composed largely of axons of the hypothalamic neurons, with the cell bodies of the neurons synthesizing oxytocin and antidiuretic hormone (ADH), also known as vasopressin.Recent studies suggest that hypoxia is a strong regulator of the function of both adeno-and neuro-hypophysis, presumably by regulating transcription of hormone mRNA through specific receptor activation (2, 3). Both protracted and intermittent hypoxia have been implicated in the regulation of hypophesial function (4-7). Hypoxia inducible factor 1α and 2α are principal transcription factor sensors of hypoxia (8). The α-subunits in the cytoplasm of cells dimerize with the β-subunit, enter the nuclei and exert their transcriptional activity on a large number of genes, including the key angiogenesis involved gene VEGF (9) and a variety of genes involved in glycolysis, metabolism, cell cycle and death pathways (10, 11).In the current study, we investigated the vascular density and the expression of HIF1α, HIF2α and VEGF in the adenohypophysis and neurohypophysis of patients deceased from various acute or chronic diseases, in order to assess whether death patterns involving hypoxia have an effect on the hypophyseal sensing of hypoxic conditions. Materials and MethodsPituitary glands from 97 cadavars were collected at autopsy. The study has been approved by the local Ethics and Research Committees. The procedure involved opening the sellar diaphragm and fracturing the dorsum of the sella turcica to allow the gland to 185

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Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent corticosterone production during hypoxia

2013

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We have previously demonstrated that the neonatal corticosterone response to acute hypoxia shifts from ACTH independence to ACTH dependence between postnatal days two (PD2) and eight (PD8). Cyclic AMP (cAMP) is the obligatory intracellular second messenger of ACTH action, and we hypothesized that corticosterone production in neonatal rats shifts from a cAMP-independent mechanism to cAMP-dependent mechanism between PD2 and PD8. Plasma ACTH and corticosterone and adrenal cAMP and cGMP responses to acute severe hypoxia (8% O2 for 5, 10, 20, 30, and 180 min) were measured in neonatal rats at PD2, PD8, and PD15. Plasma ACTH and corticosterone were measured by radioimmunoassay, and adrenal cAMP and cGMP were measured by ELISA. Plasma corticosterone-binding globulin (CBG) was measured in normoxic pups by ELISA. The largest corticosterone response was observed in PD2 pups, despite only a small increase in plasma ACTH that was not sustained. The PD2 ACTH-independent increase in corticosterone occurred with no change in adrenal cAMP or cGMP content. Plasma CBG concentration was lowest in PD2 pups. Large corticosterone responses were measured during the first 30 min of hypoxia. Differences in corticosterone responses between PD2 and PD8 pups cannot be attributed to changes in plasma protein binding capacity, and the PD2 corticosterone response is consistent with a nongenomic mechanism of action. We conclude that the sustained corticosterone response to hypoxia in PD2 pups occurs with small and transient ACTH responses and independently of increases in adrenal cAMP or cGMP.

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Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

Cited by 40 publications

References 64 publications

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

Hypoxia Inducible Factor Expression and Angiogenesis – Analysis in the Pituitary Gland and Patterns of Death

Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent corticosterone production during hypoxia

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