Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and hypothalamo-pituitary-adrenal axis

2005 ◽  
Vol 288 (2) ◽  
pp. E422-E429 ◽  
Author(s):  
Karen E. Inouye ◽  
Owen Chan ◽  
Jessica T. Y. Yue ◽  
Stephen G. Matthews ◽  
Mladen Vranic
Keyword(s):  
Diabetic Rats ◽  
Hyperinsulinemic Hypoglycemia ◽  
Mrna Levels ◽  
Sympathoadrenal System ◽  
Adrenal Axis ◽  
Basal Expression ◽  
Pomc Mrna ◽  
Recurrent Hypoglycemia ◽  
Pituitary Adrenal Axis ◽  
Th Mrna

Epinephrine, norepinephrine, and corticosterone responses to hypoglycemia are impaired in diabetic rats. Recurrent hypoglycemia further diminishes epinephrine responses. This study examined the sympathoadrenal system and hypothalamo-pituitary-adrenal axis for molecular adaptations underlying these defects. Groups were normal (N) and diabetic (D) rats and diabetic rats exposed to 4 days of 2 episodes/day of hyperinsulinemic hypoglycemia (D-hypo) or hyperinsulinemic hyperglycemia (D-hyper). D-hypo and D-hyper rats differentiated effects of hypoglycemia and hyperinsulinemia. Adrenal tyrosine hydroxylase (TH) mRNA was reduced ( P < 0.05 vs. N) 25% in all diabetic groups. Remarkably, mRNA for phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine, was reduced ( P < 0.05 vs. all) 40% only in D-hypo rats. Paradoxically, dopamine β-hydroxylase mRNA was elevated ( P < 0.05 vs. D, D-hyper) in D-hypo rats. Hippocampal mineralocorticoid receptor (MR) mRNA was increased ( P < 0.05 vs. N) in all diabetic groups. Hippocampal glucocorticoid receptor (GR), hypothalamic paraventricular nucleus (PVN) GR and corticotropin-releasing hormone (CRH), and pituitary GR and proopiomelanocortin (POMC) mRNA levels did not differ. We conclude that blunted corticosterone responses to hypoglycemia in diabetic rats are not due to altered basal expression of GR, CRH, and POMC in the hippocampus, PVN, and pituitary. The corticosterone defect also does not appear to be due to increased hippocampal MR, since we have reported normalized corticosterone responses in D-hypo and D-hyper rats. Furthermore, impaired epinephrine counterregulation in diabetes is associated with reduced adrenal TH mRNA, whereas the additional epinephrine defect after recurrent hypoglycemia is associated with decreases in both TH and PNMT mRNA.

scholarly journals Effects of Insulin Treatment without and with Recurrent Hypoglycemia on Hypoglycemic Counterregulation and Adrenal Catecholamine-Synthesizing Enzymes in Diabetic Rats

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1860-1870 ◽  
Author(s):  
Karen E. Inouye ◽  
Jessica T. Y. Yue ◽  
Owen Chan ◽  
Tony Kim ◽  
Eitan M. Akirav ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Hyperinsulinemic Hypoglycemia ◽  
Mrna Levels ◽  
Relevant Model ◽  
Counterregulatory Hormones ◽  
Catecholamine Synthesizing Enzymes ◽  
Recurrent Hypoglycemia ◽  
Th Mrna

Untreated diabetic rats show impaired counterregulation against hypoglycemia. The blunted epinephrine responses are associated with reduced adrenomedullary tyrosine hydroxylase (TH) mRNA levels. Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA. This study investigated the adaptations underlying impaired counterregulation in insulin-treated diabetic rats, a more clinically relevant model. We studied the effects of insulin treatment on counterregulatory hormones and adrenal catecholamine-synthesizing enzymes and adaptations after recurrent hypoglycemia. Groups included: normal; diabetic, insulin-treated for 3 wk (DI); and insulin-treated diabetic exposed to seven episodes (over 4 d) of hyperinsulinemic-hypoglycemia (DI-hypo) or hyperinsulinemic-hyperglycemia (DI-hyper). DI-hyper rats differentiated the effects of hyperinsulinemia from those of hypoglycemia. On d 5, rats from all groups were assessed for adrenal catecholamine-synthesizing enzyme levels or underwent hypoglycemic clamps to examine counterregulatory responses. Despite insulin treatment, fasting corticosterone levels remained increased, and corticosterone responses to hypoglycemia were impaired in DI rats. However, glucagon, epinephrine, norepinephrine, and ACTH counterregulatory defects were prevented. Recurrent hypoglycemia in DI-hypo rats blunted corticosterone but, surprisingly, not epinephrine responses. Norepinephrine and ACTH responses also were not impaired, whereas glucagon counterregulation was reduced due to repeated hyperinsulinemia. Insulin treatment prevented decreases in basal TH protein and increased PNMT and dopamine β-hydroxylase protein. DI-hypo rats showed increases in TH, PNMT, and dopamine β-hydroxylase. We conclude that insulin treatment of diabetic rats protects against most counterregulatory defects but not elevated fasting corticosterone and decreased corticosterone counterregulation. Protection against epinephrine defects, both without and with antecedent hypoglycemia, is associated with enhancement of adrenal catecholamine-synthesizing enzyme levels.

scholarly journals Corticosterone-induced negative feedback mechanisms within the hypothalamo–pituitary–adrenal axis of the chicken

2005 ◽  
Vol 185 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Kristien Vandenborne ◽  
Bert De Groef ◽  
Sofie M E Geelissen ◽  
Eduard R Kühn ◽  
Veerle M Darras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Feedback Inhibition ◽  
Mrna Levels ◽  
Hypothalamic Area ◽  
Adrenal Axis ◽  
Pomc Mrna ◽  
Pituitary Adrenal Axis

This paper reports the results of in vivo and in vitro experiments on the feedback effects of corticosterone on the hypothalamo–pituitary–adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 μg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivo administration of corticosterone. In vitro, incubation with 1 μM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitro effects were the same at the two ages studied. The in vitro feedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

Hormones, stress and the welfare of animals

2018 ◽  
Vol 58 (3) ◽  
pp. 408 ◽  
Author(s):  
A. J. Tilbrook ◽  
C. R. Ralph
Keyword(s):  
Stress Responses ◽  
Sympathoadrenal System ◽  
Hormonal Responses ◽  
Positive Effects ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

There are numerous endocrine (hormonal) responses during stress and these are often complex. This complexity makes the study of endocrine stress responses challenging and the challenges are intensified when attempts are made to use measures of hormones to assess the welfare of animals because so many endocrine systems are activated during stress and because there are countless stimuli that trigger these systems. Most research has concentrated on only a small number of these endocrine systems, particularly the hypothalamo–pituitary adrenal axis and the sympathoadrenal system, and there is a need to broaden the scope of endocrine systems that are studied. Furthermore, systematic approaches are required to establish when the actions of hormones associated with stress responses result in physiological and/or behavioural consequences that will have negative or positive effects on the welfare of animals.

scholarly journals Effects of Maternal Dexamethasone Treatment in Early Pregnancy on Pituitary-Adrenal Axis in Fetal Sheep

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5466-5477 ◽  
Author(s):  
Thorsten Braun ◽  
Shaofu Li ◽  
Deborah M. Sloboda ◽  
Wei Li ◽  
Melanie C. Audette ◽  
...  
Keyword(s):  
Plasma Cortisol ◽  
Developmental Trajectory ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Fetal Sheep ◽  
Total N ◽  
Hypothalamic Pituitary Adrenal ◽  
Fetal Plasma ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

Abstract Fetal exposure to elevated levels of bioactive glucocorticoids early in gestation, as in suspected cases of congenital adrenal hyperplasia, may result in adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and function may be involved. We investigated immediate and long-term effects of maternal dexamethasone (DEX) administration early in pregnancy on fetal growth and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated groups (im injections of 0.14 mg/kg ewe weight · 12 h) at 40–41 d gestation (dG). At 50, 100, 125, and 140 dG, fetal plasma and tissues were collected. DEX-exposed fetuses were lighter than controls at 100 dG (P &lt; 0.05) but not at any other times. Fetal plasma ACTH levels and pituitary POMC and PC-1 mRNA levels were similar between groups. Fetal plasma cortisol levels were significantly reduced after DEX exposure in both male and female fetuses at 50 dG (P &lt; 0.05), were similar at 100 and 125 dG, but were significantly higher than controls at 140 dG. At 140 dG, there was increased adrenal P450C17 and 3β-HSD mRNA in female fetuses and reduced expression of ACTH-R mRNA in males. Fetal hepatic CBG mRNA levels mimicked plasma cortisol patterns. DEX exposure reduced CBG only in males at 50 dG (P &lt; 0.05). Placental mRNA levels of 11β-HSD2 were increased after DEX in males (P &lt; 0.05). Therefore, in sheep, early DEX may alter the developmental trajectory of the fetal hypothalamic-pituitary-adrenal axis, directly increasing fetal adrenal activation but not anterior pituitary function. In females, this effect may be attributed, in part, to increased fetal adrenal steroidogenic activity.

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