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 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 Psychosocial Stress Inhibits Amplitude of Gonadotropin-Releasing Hormone Pulses Independent of Cortisol Action on the Type II Glucocorticoid Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 762-769 ◽  
Author(s):  
Elizabeth R. Wagenmaker ◽  
Kellie M. Breen ◽  
Amy E. Oakley ◽  
Alan J. Tilbrook ◽  
Fred J. Karsch
Keyword(s):  
Glucocorticoid Receptor ◽  
Psychosocial Stress ◽  
Pulse Amplitude ◽  
Cortisol Secretion ◽  
Type Ii ◽  
Predator Cues ◽  
Pulsatile Gnrh ◽  
Gnrh Release ◽  
Hormone Pulses ◽  
Antagonist Ru486

Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold, and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different. A paradigm of psychosocial stress inhibits GnRH pulse amplitude. This effect is not reversed by treatment with RU486, a type II glucocorticoid receptor antagonist.

scholarly journals Oxidized Lipoproteins Suppress Nitric Oxide Synthase in Macrophages: Study of Glucocorticoid Receptor Involvement

1994 ◽  
Vol 3 (5) ◽  
pp. 323-327 ◽  
Author(s):  
K. E. Matthys ◽  
P. G. Jorens ◽  
B. Marescau ◽  
M. Rosseneu ◽  
H. Bult ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glucocorticoid Receptor ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Inos Activity ◽  
Atherosclerotic Lesions ◽  
Oxidized Lipoproteins ◽  
Oxide Synthase

Activated cholesterol-laden macrophages in atherosclerotic lesions are believed to influence the progression of this disease. The induction of nitric oxide synthase (iNOS) activity was investigated in control and cholesterol-laden J774 macrophages, obtained by pre-incubation with oxidized or acetylated low density lipoproteins (oxLDL, acLDL). Loading with oxLDL caused a small induction of NOS activity in unstimulated cells, as indicated by nitrite and citrulline accumulation in the supernatant. However, it suppressed the iNOS activity resulting from stimulation of the cells with lipopolysaccharide with or without interferon-γ. AcLDL had no inhibitory effect, indicating that cholesterol accumulation as such was not responsible. Since the induction of NOS in macrophages is inhibited by glucocorticoids, the possibility that a glucocorticoid-like factor, formed during oxidation of LDL, may cause the inhibition, was investigated. However, addition of the glucocorticoid receptor antagonist mifepristone did not prevent the oxLDL-dependent NOS inhibition, indicating that the glucocorticoid receptor is not involved in the suppressive effect of oxLDL.

scholarly journals Regulation of corticosteroid receptors in patients with anorexia nervosa and Cushing's syndrome

1998 ◽  
Vol 158 (3) ◽  
pp. 435-439 ◽  
Author(s):  
D Armanini ◽  
P Spinella ◽  
M Simoncini ◽  
A Basso ◽  
S Zovato ◽  
...  
Keyword(s):  
Weight Loss ◽  
Anorexia Nervosa ◽  
Cushing’S Syndrome ◽  
Plasma Cortisol ◽  
Cushing's Syndrome ◽  
Mononuclear Leukocytes ◽  
Type I ◽  
Healthy Controls ◽  
Type Ii ◽  
Corticosteroid Receptors

We have studied 16 patients with anorexia nervosa (11 with a stabilised weight loss and 5 in the weight-losing phase), 11 healthy controls, and 10 patients with Cushing's syndrome, by measuring plasma cortisol (by enzyme-immunoassay), ACTH (by RIA), corticosteroid (Type I-mineralocorticoid and Type II-glucocorticoid) receptors in mononuclear leukocytes (by radio-receptor assay), and lymphocyte subpopulations (by cytofluorimetry). In anorexic patients with a stabilised weight loss and in Cushing's syndrome the mean value of both Type I and Type II corticosteroid receptors in mononuclear leukocytes was significantly lower than in controls. The correlation between Type II receptors and plasma cortisol was inverse in stabilised anorexia nervosa and in Cushing's syndrome, and direct in healthy controls. Anorexic patients in the weight-losing phase showed a significant increase in plasma cortisol levels and a normal number of Type II receptors. From these results we hypothesise that in anorexia nervosa there is a progression from an increase in plasma cortisol in the weight-losing phase, to a concomitant decrease in Type II receptors when the disease is stabilised.

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

scholarly journals Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment

Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2639-2649 ◽  
Author(s):  
Adam J. Pawson ◽  
Stuart Maudsley ◽  
Kevin Morgan ◽  
Lindsay Davidson ◽  
Zvi Naor ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Type I ◽  
Type Ii ◽  
Gene Fragment ◽  
Releasing Hormone ◽  
Human Type ◽  
Gonadotropin Releasing Hormone Receptor

scholarly journals Excitability and Threshold Mechanism for Enhanced Neuronal Response Induced by Inhibition Preceding Excitation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Hanqing Ma ◽  
Bing Jia ◽  
Yuye Li ◽  
Huaguang Gu
Keyword(s):  
Steady State ◽  
Neuronal Response ◽  
Inhibitory Effect ◽  
Type I ◽  
Type Ii ◽  
Neural Firing ◽  
Firing Activity ◽  
Subthreshold Oscillations ◽  
Auditory Nervous System ◽  
Threshold Mechanism

Postinhibitory facilitation (PIF) of neural firing presents a paradoxical phenomenon that the inhibitory effect induces enhancement instead of reduction of the firing activity, which plays important roles in sound location of the auditory nervous system, awaited theoretical explanations. In the present paper, excitability and threshold mechanism for the PIF phenomenon is presented in the Morris-Lecar model with type I, II, and III excitabilities. Firstly, compared with the purely excitatory stimulations applied to the steady state, the inhibitory preceding excitatory stimulation to form pairs induces the firing rate increased for type II and III excitabilities instead of type I excitability, when the interval between the inhibitory and excitatory stimulation within each pair is suitable. Secondly, the threshold mechanism for the PIF phenomenon is acquired. For type II and III excitabilities, the inhibitory stimulation induces subthreshold oscillations around the steady state. During the middle and ending phase of the ascending part and the beginning phase of the descending part within a period of the subthreshold oscillations, the threshold to evoke an action potential by an excitatory stimulation becomes weaker, which is the cause for the PIF phenomenon. Last, a theoretical estimation for the range of the interval between the inhibitory and excitatory stimulation for the PIF phenomenon is acquired, which approximates half of the intrinsic period of the subthreshold oscillations for the relatively strong stimulations and becomes narrower for the relatively weak stimulations. The interval for the PIF phenomenon is much shorter for type III excitability, which is closer to the experiment observation, due to the shorter period of the subthreshold oscillations. The results present the excitability and threshold mechanism for the PIF phenomenon, which provide comprehensive and deep explanations to the PIF phenomenon.

scholarly journals Antiprogestins RU486 and ZK299 suppress basal and LHRH-stimulated FSH and LH secretion at pituitary level in the rat in an oestrous cycle stage-dependent manner

1999 ◽  
Vol 163 (1) ◽  
pp. 79-85 ◽  
Author(s):  
C Bellido ◽  
D Gonzalez ◽  
R Aguilar ◽  
JE Sanchez-Criado
Keyword(s):  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Type I ◽  
Dependent Manner ◽  
Natural Ligand ◽  
Ovx Rats ◽  
20 Nm ◽  
Lh Secretion

We have previously shown that administration of antiprogestin (AP) type II RU486 to ovariectomized (OVX) rats on the morning of pro-oestrus decreases the magnitude of preovulatory gonadotrophin surge. This suggests that the effect of RU486 on LHRH-dependent gonadotrophin release may be independent of its ability to block progesterone actions. The aim of the present research was to study the possible site of RU486 action and to determine whether the gonadotrophin suppressive effect of APs RU486 and ZK299 is dependent on the oestrogen background. Intact or OVX rats in the morning of pro-oestrus were injected s.c. with 4 mg of RU486 or ZK299 (AP type I) at 0900 h on pro-oestrus. At 1830 h, serum concentration of FSH and LH and median eminence (ME) content of LHRH were determined. In the second experiment, the effect of RU486 and ZK299 on pituitary responsiveness to LHRH (100 ng, i.p.) and ME content of LHRH at 1830 h pentobarbital-blocked intact or OVX rats was evaluated. In the last study, the anterior pituitary release of FSH and LH from pro-oestrus or metoestrus donors incubated with or without LHRH (1, 10 or 100 nM) in the presence or absence of APs (20 nM) was evaluated. Both APs reduced serum FSH and LH levels at 1830 h on pro-oestrus in intact and OVX rats. The suppressive effect on gonadotrophin release brought about by AP treatment was also evidenced in PB-blocked intact and OVX rats. This suggested that the inhibitory effect of APs occurred, at least in part, at pituitary level. Furthermore, in the absence of the natural ligand, APs significantly reduced basal and LHRH-stimulated FSH and LH release from pro-oestrous but not from metoestrus pituitaries. In conclusion, these experiments have shown, both 'in vivo' and 'in vitro', that APs RU486 and ZK299 have suppressive effects at pituitary level on basal and LHRH-stimulated FSH and LH secretion, regardless of their antiprogestagenic activity, in pro-oestrus but not in metoestrus.

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