scholarly journals Effects of corticosteroids on urinary ammonium excretion in humans.

1994 ◽  
Vol 4 (8) ◽  
pp. 1531-1537
Author(s):  
M M Waybill ◽  
J N Clore ◽  
R A Emerick ◽  
C O Watlington ◽  
A C Schoolwerth
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Steroid Hormones ◽  
Serum Potassium ◽  
Mineralocorticoid Receptor ◽  
Normal Male ◽  
Type I ◽  
Ammonium Excretion ◽  
Type Ii ◽  
Selective Effects

This study was designed to examine the selective effects of glucocorticoid and mineralocorticoid classes of steroid hormones on urinary ammonium excretion in humans. In 22 10-day studies, normal male volunteers received either 9 alpha-fludrohydrocortisone or hydrocortisone, alone or with the receptor antagonist spironolactone or mifepristone. The small but significant increase in ammonium excretion noted with the administration of 9 alpha-fludrohydrocortisone was associated with a significant decrease in serum potassium. In contrast, a significantly larger increase in ammonium excretion was noted with hydrocortisone, without concomitant electrolyte changes. Spironolactone did not alter the effect on ammonium excretion by either corticosteroid, whereas mifepristone markedly blunted the hydrocortisone-induced increase in urinary ammonium excretion. It was concluded that glucocorticoids increase urinary ammonium excretion in humans and that this effect occurs through binding to the Type II (glucocorticoid) receptor rather than by cross-occupancy of the Type I (mineralocorticoid) receptor.

scholarly journals Does the Type II Glucocorticoid Receptor Mediate Cortisol-Induced Suppression in Pituitary Responsiveness to Gonadotropin-Releasing Hormone?

Endocrinology ◽  
2004 ◽  
Vol 145 (6) ◽  
pp. 2739-2746 ◽  
Author(s):  
Kellie M. Breen ◽  
Catherine A. Stackpole ◽  
Iain J. Clarke ◽  
Andrew V. Pytiak ◽  
Alan J. Tilbrook ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mineralocorticoid Receptor ◽  
Plasma Cortisol ◽  
Pulse Amplitude ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Gonadotropin Releasing Hormone ◽  
Type I ◽  
Type Ii ◽  
Pulsatile Gnrh

Abstract Stress-like elevations in plasma cortisol suppress LH pulse amplitude in ovariectomized ewes by inhibiting pituitary responsiveness to GnRH. Here we sought to identify the receptor mediating this effect. In a preliminary experiment GnRH and LH pulses were monitored in ovariectomized ewes treated with cortisol plus spironolactone, which antagonizes the type I mineralocorticoid receptor (MR), or with cortisol plus RU486, which antagonizes both the type II glucocorticoid receptor (GR) and the progesterone receptor (PR). Cortisol alone reduced LH pulse amplitude, but not pulsatile GnRH secretion, indicating that it reduced pituitary responsiveness to endogenous GnRH. RU486, but not spironolactone, reversed this suppression. We next tested whether RU486 reverses the inhibitory effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, frequency, and duration. Hourly GnRH pulses were delivered to ovariectomized ewes in which endogenous GnRH pulses were blocked by estradiol during seasonal anestrus. Cortisol alone reduced the amplitude of LH pulses driven by the exogenous GnRH pulses. RU486, but not an antagonist of PR (Organon 31710), prevented this suppression. Thus, the efficacy of RU486 in blocking the suppressive effect of cortisol is attributed to antagonism of GR, not PR. Together, these observations imply that the type II GR mediates cortisolinduced suppression of pituitary responsiveness to GnRH.

scholarly journals The Mineralocorticoid Receptor Antagonist Eplerenone Suppress Interstitial Fibrosis in Subcutaneous Adipose Tissue in Type 2 Diabetes Patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Marie Louise Johansen ◽  
Jaime Ibarrola ◽  
Amaya Fernández-Celis ◽  
Morten Schou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Subcutaneous Adipose Tissue ◽  
Mineralocorticoid Receptor ◽  
Prostaglandin D2 ◽  
Type I ◽  
Mineralocorticoid Receptor Antagonist ◽  
Subcutaneous Adipose

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association between the MR, fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present sub-study including 30 participants was prespecified as part of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, randomizing patients to either high dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examinations and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen type I and VI, and the profibrotic factor α-smooth muscle actin, as compared to placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase–associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusions, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

scholarly journals Hypothalamic-Pituitary-Adrenal Axis Activity of Newborn Mice Rapidly Desensitizes to Repeated Maternal Absence but Becomes Highly Responsive to Novelty

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6366-6377 ◽  
Author(s):  
L. Enthoven ◽  
M. S. Oitzl ◽  
N. Koning ◽  
M. van der Mark ◽  
E. R. de Kloet
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Hpa Axis ◽  
Mineralocorticoid Receptor ◽  
Maternal Separation ◽  
Mineralocorticoid Receptor Antagonist ◽  
Newborn Mice ◽  
Hypothalamic Pituitary Adrenal ◽  
The Third ◽  
Corticosterone Response

In CD1 mice we investigated the hypothalamic-pituitary-adrenal (HPA) axis response to maternal separation for 8 h daily from postnatal d 3 to 5. At d 3 a slow separation-induced corticosterone response developed that peaked after 8 h, and the pups became responsive to stressors. On the second and third day, the response to 8 h separation rapidly attenuated, whereas the response to novelty did not, a pattern reflected by the hypothalamic c-fos mRNA response. If maternal separation and exposure to novelty were combined, then after the third such daily exposure, the sensitivity to the stressor was further enhanced. Meanwhile, basal corticosterone and ACTH levels were persistently suppressed 16 h after pups were reunited with their mothers. To explain the HPA axis desensitization after repeated separation, we found that circulating ghrelin levels increased and glucose levels decreased after all periods of maternal separation, ruling out a role of altered metabolism. Glucocorticoid feedback was not involved either because a glucocorticoid receptor antagonist amplified the corticosterone response after the first but became ineffective after the third separation. In contrast, a mineralocorticoid receptor antagonist decreased and increased corticosterone levels after the first and third period of separation, respectively. In conclusion, the newborn’s HPA axis readily desensitizes to repeated daily maternal separation, but continues to respond to novelty in a manner influenced by a central mineralocorticoid receptor- rather than glucocorticoid receptor-mediated mechanism.

Effects of adrenalectomy and type I or type II glucocorticoid receptor activation on 5-HT1A and 5-HT2 receptor binding and 5-HT transporter mRNA expression in rat brain

1994 ◽  
Vol 648 (1) ◽  
pp. 157-161 ◽  
Author(s):  
Yasukazu Kuroda ◽  
Yoshifumi Watanabe ◽  
David S. Albeck ◽  
Nicholas B. Hastings ◽  
Bruce S. McEwen
Keyword(s):  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Rat Brain ◽  
Receptor Binding ◽  
Receptor Activation ◽  
Type I ◽  
Type Ii

Effects of adrenalectomy and Type I or Type II glucocorticoid receptor activation on AVP and CRH mRNA in the rat hypothalamus

1994 ◽  
Vol 26 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
David S. Albeck ◽  
Nicholas B. Hastings ◽  
Bruce S. McEwen
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Activation ◽  
Type I ◽  
Type Ii ◽  
Rat Hypothalamus

scholarly journals Role of endogenous PACAP in catecholamine secretion from the rat adrenal gland

2001 ◽  
Vol 281 (5) ◽  
pp. R1562-R1567 ◽  
Author(s):  
Yasuo Fukushima ◽  
Hirohiko Hikichi ◽  
Kazuhiko Mizukami ◽  
Takahiro Nagayama ◽  
Makoto Yoshida ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Adrenal Gland ◽  
Adenylate Cyclase ◽  
Receptor Antagonist ◽  
Catecholamine Secretion ◽  
Type I ◽  
Type Ii ◽  
Low Concentrations ◽  
Pituitary Adenylate Cyclase

We elucidated the contribution of endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) to neurally evoked catecholamine secretion from the isolated perfused rat adrenal gland. Infusion of PACAP (100 nM) increased adrenal epinephrine and norepinephrine output. The PACAP-induced catecholamine output responses were inhibited by the PACAP type I receptor antagonist PACAP- (6-38) (30–3,000 nM) but were resistant to the PACAP type II receptor antagonist [Lys1,Pro2,5,Ara3,4,Tyr6]-vasoactive intestinal peptide (LPAT-VIP; 30–3,000 nM). Transmural electrical stimulation (ES; 1–10 Hz) or infusion of ACh (6–200 nM) increased adrenal epinephrine and norepinephrine output. PACAP-(6–38) (3,000 nM), but not LPAT-VIP, also inhibited the ES-induced catecholamine output responses. However, PACAP-(6–38) did not affect the ACh-induced catecholamine output responses. PACAP at low concentrations (0.3–3 nM), which had no influence on catecholamine output, enhanced the ACh-induced catecholamine output responses, but not the ES-induced catecholamine output responses. These results suggest that PACAP is released from the nerve endings to facilitate the neurally evoked catecholamine secretion through PACAP type I receptors in the rat adrenal gland.

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