scholarly journals Anterior pituitary trophic responses to dexamethasone withdrawal and repeated dexamethasone exposures

2001 ◽  
Vol 169 (2) ◽  
pp. 263-270 ◽  
Author(s):  
LA Nolan ◽  
A Levy
Keyword(s):  
Hpa Axis ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Duration Of Treatment ◽  
Glucocorticoid Treatment ◽  
Initial Exposure ◽  
Male Wistar Rats ◽  
Anatomic Basis ◽  
Delayed Recovery ◽  
Trophic Responses

Glucocorticoid withdrawal, depending on the dose and duration of treatment, results in a transient but sometimes prolonged reduction in hypothalamo-pituitary-adrenal (HPA) axis secretory responsiveness. As the anatomic basis of HPA axis suppression remains uncertain, we have directly examined changes in trophic activity within the rat anterior pituitary gland following dexamethasone withdrawal and re-treatment. Treatment of adrenalectomised, male Wistar rats with dexamethasone results in a discrete, highly significant burst of apoptosis in the anterior pituitary with concurrent suppression of mitosis. Despite a surge in mitotic activity immediately after dexamethasone withdrawal, calculated total anterior pituitary cell populations remain below that seen in untreated adrenalectomised controls. Repeated exposures to dexamethasone show that the dexamethasone-sensitive cell population that is deleted by apoptosis is partially but not completely restored. As the amplitude of apoptotic bursts induced by second and third dexamethasone exposures are similar but smaller than that induced by initial exposure, it appears that the very first exposure to dexamethasone deletes a subset of anterior pituitary cells that are either not restored at all, or are only replaced very slowly. The reduced proportion of corticotrophs contributing to the increase in mitotic index after dexamethasone withdrawal corroborates this. Although continued cell turnover within the pituitary predicts that the absolute cellular deficit would diminish with time, the effects seen may contribute to the delayed recovery of pituitary axis function following cessation of glucocorticoid treatment.

scholarly journals Cocaine- and Amphetamine-Regulated Transcript Activates the Hypothalamic-Pituitary-Adrenal Axis through a Corticotropin-Releasing Factor Receptor-Dependent Mechanism

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5202-5209 ◽  
Author(s):  
Sean M. Smith ◽  
Joan M. Vaughan ◽  
Cynthia J. Donaldson ◽  
Jean Rivier ◽  
Chien Li ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Anterior Pituitary ◽  
Corticotropin Releasing Factor ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Anterior Pituitary Cells ◽  
Circulating Levels ◽  
Dependent Mechanism ◽  
Acth Release

Abstract Cocaine- and amphetamine-regulated transcript (CART) is a highly expressed hypothalamic transcript that is concentrated in areas associated with the stress response. There is evidence for a role of CART in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear whether CART regulates activity of the HPA axis by directly stimulating ACTH release from pituitary corticotropes or through interaction with hypothalamic factors. To address this issue, the effects of central and peripheral administration of CART on the HPA axis were compared. Central administration of CART(55–102) (1 μg) significantly increased circulating levels of ACTH (481 ± 122 vs. 93 ± 14 pg/ml; CART vs. vehicle) and corticosterone (460 ± 29 vs. 179 ± 62 ng/ml; CART vs. vehicle). In contrast, iv injection of CART(55–102) (0.09-9.0 nmol/kg) did not significantly affect circulating levels of ACTH or corticosterone. The corticotropin-releasing factor (CRF) receptor antagonist Astressin B was used to determine whether CART(55–102) elicits ACTH secretion via a CRF receptor-dependent mechanism. Injection of Astressin B (50 μg/kg, iv) inhibited CART(55–102)-induced ACTH and corticosterone responses. The effects of CART(55–102) on CRF and arginine vasopressin (AVP) expression were also examined in static hypothalamic explants. RT-PCR analysis revealed a significant up-regulation of CRF and AVP mRNA levels after CART(55–102) (10 nm and 1 μm) treatment. Last, the effects of CART(55–102) on CRF- and AVP-mediated ACTH release was investigated in dispersed rat anterior pituitary cells. Incubation of CART(55–102) (10–100 nm) did not significantly affect ACTH release from anterior pituitary cells. Findings from the present study suggest that CART regulates activity of the HPA axis through a CRF-dependent central mechanism and not by means of direct interaction with pituitary corticotropes.

A COMPARISON OF THE EFFECTS OF FOUR ERGOT DERIVATIVES ON PROLACTIN SECRETION BY DISPERSED RAT PITUITARY CELLS

1980 ◽  
Vol 87 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G. DELITALA ◽  
T. YEO ◽  
ASHLEY GROSSMAN ◽  
N. R. HATHWAY ◽  
G. M. BESSER
Keyword(s):  
Anterior Pituitary ◽  
Ergot Alkaloids ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Inhibitory Effects ◽  
Prolactin Release ◽  
Ergot Derivatives ◽  
Rat Pituitary ◽  
Rat Pituitary Cells

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2·3; bromocriptine, 13; lisuride, 15; pergolide, 23. The dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.

Tyrosine kinase inhibitors enhance GHRH-stimulated cAMP accumulation and GH release in rat anterior pituitary cells

1997 ◽  
Vol 152 (2) ◽  
pp. 193-199 ◽  
Author(s):  
T Ogiwara ◽  
C L Chik ◽  
A K Ho
Keyword(s):  
Tyrosine Kinase ◽  
Cholera Toxin ◽  
Tyrosine Kinase Inhibitors ◽  
Anterior Pituitary ◽  
Kinase Inhibitors ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Anterior Pituitary Cells ◽  
Site Of Action

Abstract In this study, the role of tyrosine phosphorylation in agonist-stimulated cAMP accumulation and GH release in rat anterior pituitary cells was investigated. It was found that genistein, a tyrosine kinase inhibitor, while having no effect on its own, potentiated GHRH-stimulated cAMP accumulation in a concentration-dependent manner. In comparison, daidzein, an inactive analogue of genistein, was ineffective and vanadate, a phosphotyrosine phosphatase inhibitor, reduced GHRH-stimulated cAMP accumulation. Additional structurally unrelated tyrosine kinase inhibitors, erbstatin and tyrphostins, also potentiated GHRH-stimulated cAMP accumulation. To determine the site of action of the tyrosine kinase inhibitors, pituitary adenylate cyclase-activating polypeptide (PACAP), cholera toxin and forskolin were used to increase cAMP accumulation. Genistein enhanced the PACAP-, cholera toxin- or forskolin-stimulated cAMP accumulation, suggesting that the site of action is at the post-receptor level. However, when the phosphodiesterase was inhibited by isobutylmethylxanthine, genistein did not potentiate and vanadate did not inhibit GHRH-stimulated cAMP accumulation, indicating that phosphodiesterase is a probable site of action for the inhibitor. Genistein and erbstatin also enhanced GHRH-stimulated GH release and the effect of vanadate was inhibitory. These results indicate that tyrosine kinase inhibitors enhance cAMP accumulation through their action on phosphodiesterase activity in rat anterior pituitary cells and the tyrosine kinase pathway appears to be involved in the control of GH release. Journal of Endocrinology (1997) 152, 193–199

Culture of Enzymatically Dispersed Anterior Pituitary Cells: Functional Validation of a Method

Endocrinology ◽  
1972 ◽  
Vol 91 (2) ◽  
pp. 562-572 ◽  
Author(s):  
WYLIE VALE ◽  
GEOFFREY GRANT ◽  
MAX AMOSS ◽  
RICHARD BLACKWELL ◽  
ROGER GUILLEMIN
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Functional Validation ◽  
Anterior Pituitary Cells

Substance P stimulation of polyphosphoinositide hydrolysis in rat anterior pituitary membranes involves a GTP-dependent mechanism

1991 ◽  
Vol 130 (1) ◽  
pp. 63-70 ◽  
Author(s):  
S. E. Mau ◽  
T. Saermark
Keyword(s):  
Substance P ◽  
Pertussis Toxin ◽  
Anterior Pituitary ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Sodium Deoxycholate ◽  
Pituitary Cells ◽  
Guanine Nucleotide ◽  
Nk1 Receptor ◽  
Gtp Binding

ABSTRACT Substance P (SP) stimulates polyphosphoinositide breakdown in the rat anterior pituitary through an NK-1 receptor. In the present study we present evidence that the coupling between the SP–NK1 receptor complex and polyphosphoinositide-specific phospholipase C (PI-PLC) in rat anterior pituitary membranes may involve a mechanism consistent with a GTP-binding protein. The formation of inositol phosphates from [3H]myo-inositol-labelled anterior pituitary membranes induced by SP was potentiated by GTP and non-hydrolysable guanine nucleotides. The stimulatory effects of SP alone and SP plus GTP could be blocked by addition of GDP-β-S (guanosine 5-O-(thiodiphosphate)) in excess. Basal and SP plus guanine nucleotide-induced inositol phosphate formation were stimulated by fluoride, whereas the effect of SP alone was inhibited. Pretreatment of anterior pituitary membranes with sodium deoxycholate attenuated the inositol phosphate response elicited by GTP and GTP-γ-S, whereas basal and SP-stimulated inositol phosphate production showed a peak at 1 mg sodium deoxycholate/ml. SP, fluoride and guanine nucleotide stimulatory effects on hydrolysis of polyphosphoinositide (PPI) were unaffected by pretreatment of anterior pituitary cells with cholera or pertussis toxin for 12 h. Treatment of anterior pituitary membranes with cholera and pertussis toxin yielded [32P]ADP-ribosylation of two proteins with molecular masses of 45 and 41 kDa respectively. We conclude that SP coupling to PI-PLC through the NK1 receptor in the rat anterior pituitary involves a GTP-binding mechanism distinct from the G-proteins associated with adenylate cyclase, Gs and Gi. Journal of Endocrinology (1991) 130, 63–70

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