High concentrations of catecholamines selectively diminish the sensitivity of CRF-stimulated acth release by cultured rat pituitary cells to the suppressive effects of dexamethasone

Plasma concentrations of immunoreactive (ir)-inhibin were measured in seven pregnant mares from around Day 140 of gestation to Day 2 after parturition using a heterologous bovine-based radioimmunoassay (RIA). Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, progesterone and relaxin were also measured in the same samples. A marked increase in plasma concentrations of ir-inhibin, FSH and LH occurred between Day 220 and Day 300 of gestation but the concentrations of all three hormones returned to baseline by about Day 320 (three weeks before parturition). In contrast, circulating concentrations of the three placental hormones, oestradiol-17 beta, progesterone and relaxin, increased during the final weeks of pregnancy and then decreased markedly to basal values within two days of parturition. There was a positive correlation between circulating concentrations of ir-inhibin and FSH (r = 0.75, P < 0.01) rather than the expected negative correlation. ir-inhibin was not detected in homogenates obtained at Day 190 of pregnancy and form term placenta, but high concentrations of ir-inhibin were present in homogenates of fetal and newborn gonads. Despite the high concentrations of ir-inhibin in these homogenates, they failed to exert any suppressive bioactivity on FSH secretion by rat pituitary cells cultured in vitro. Furthermore, immunohistochemical staining revealed the presence of inhibin in the interstitial cells of equine fetal gonads at Day 190 of gestation. These findings demonstrate for the first time that high concentrations of ir-inhibin, LH and FSH are secreted into the peripheral circulation of the mare during the second half of pregnancy. However, ir-inhibin present in the plasma of pregnant mares appears to be biologically inactive. This hormone is not presumed to be of placental origin but it is proposed that either the enlarged fetal gonads or the maternal ovaries, or both of these organs, may be a source of inhibin in response to the coincident increase in circulating concentrations of LH and FSH.

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GROWTH IN MONOLAYER CULTURE OF RAT PITUITARY CELLS WHICH SYNTHETIZE AND RELEASE ACTH

Acta Endocrinologica ◽

10.1530/acta.0.0790421 ◽

1975 ◽

Vol 79 (3) ◽

pp. 421-430 ◽

Cited By ~ 2

Author(s):

R. E. Lang ◽

I. Hilwig ◽

K. H. Voigt ◽

H. L. Fehm ◽

E. F. Pfeiffer

Keyword(s):

Pituitary Gland ◽

Monolayer Culture ◽

Pituitary Cells ◽

Dependent Manner ◽

Antibody Technique ◽

Gland Cells ◽

Rat Pituitary ◽

Rat Pituitary Cells ◽

Dose Dependent ◽

Acth Release

ABSTRACT Cultures of rat pituitary gland cells were developed to study biosynthesis and release of ACTH. ACTH measurement was accomplished by radioimmunoassay. ACTH release was observed following stimulation with theophylline and cAMP in a dose-dependent manner. Biosynthesis was demonstrated by incorporation of 3H-phenylalanine into the hormone, employing a double antibody technique.

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Studies on the glucocorticoid-receptor blocking action of RU 38486 in cultured ACTH-secreting human pituitary tumour cells and normal rat pituitary cells

Acta Endocrinologica ◽

10.1530/acta.0.1090064 ◽

1985 ◽

Vol 109 (1) ◽

pp. 64-69 ◽

Cited By ~ 19

Author(s):

S. W. J. Lamberts ◽

E. G. Bons ◽

P. Uitterlinden

Keyword(s):

Pituitary Tumour ◽

Tumour Cells ◽

Pituitary Cells ◽

Human Pituitary ◽

Inhibiting Effect ◽

Rat Pituitary ◽

Normal Rat ◽

Rat Pituitary Cells ◽

Acth Secreting ◽

Acth Release

Abstract. The glucocorticoid-receptor blocking actions of RU 38486, a new compound with anti-progesterone activity, have been investigated in cultured human ACTH-secreting pituitary tumour cells and normal rat pituitary cells. Pre-incubation of human pituitary tumour cells for 24 h with RU 38486 (1 μm) did not influence basal or CRF-stimulated ACTH release. RU 38486 (100 nm–1 μm) significantly overcame or prevented the dexamethasone (100 nm–1 μm)-induced inhibition of CRF-stimulated ACTH release by the cultured tumour cells prepared from 2 patients with Cushing's disease. The tumour cells of a third patient were insensitive to CRF. Pre-incubation for 24 h with 1 μm RU 38486 facilitated CRF-stimulated ACTH release significantly. Studies with cultured normal rat pituitary cells showed that the inhibiting effect of 24 h pre-incubation with 10 and 50 nm dexamethasone on CRF-stimulated ACTH release could be acutely (measured over 4 h) overruled in a dose-dependent way by RU 38486 (100 nm, 1 and 10 μ), while pre-incubation for 24 h of these cells with RU 38486 (100 nm and 1 μm) significantly attenuated the acute inhibiting effect of 1 μm dexamethasone on CRF-stimulated ACTH-release. The results of these in vitro experiments are discussed against the background of the possible therapeutic use RU 38486 in patients with Cushing's syndrome in order to block the deleterious effects of high circulating cortisol concentrations.

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Site of inhibitory action of CRF 9-41 on ACTH release from isolated rat pituitary cells

Life Sciences ◽

10.1016/0024-3205(87)90236-0 ◽

1987 ◽

Vol 40 (12) ◽

pp. 1179-1184 ◽

Cited By ~ 7

Author(s):

Mark J. Rosenthal ◽

James C. Kraner ◽

Glenn T. Peake

Keyword(s):

Inhibitory Action ◽

Pituitary Cells ◽

Rat Pituitary ◽

Rat Pituitary Cells ◽

Isolated Rat ◽

Acth Release

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RAT MELANIN CONCENTRATING HORMONE DOES NOT MODIFY THE RELEASE OF CRH-41 FROM RAT HYPOTHALAMUS OR ACTH FROM THE ANTERIOR PITUITARY IN VITRO

Journal of Endocrinology ◽

10.1677/joe.0.127r001 ◽

1990 ◽

Vol 127 (1) ◽

pp. R1-R4 ◽

Cited By ~ 24

Author(s):

P. Navarra ◽

S. Tsagarakis ◽

D. H. Coy ◽

L.H. Rees ◽

G. M. Besser ◽

...

Keyword(s):

Inhibitory Activity ◽

Anterior Pituitary ◽

Pituitary Cells ◽

Inhibitory Effects ◽

Acth Secretion ◽

Rat Pituitary ◽

Melanin Concentrating Hormone ◽

Rat Pituitary Cells ◽

Acth Release

ABSTRACT It has been suggested that melanin concentrating hormone (MCH) possesses potent corticotrophin (ACTH) inhibitory activity, on the basis of the inhibitory effects displayed by salmon MCH on ACTH release from either trout or rat isolated pituitary fragments. Recently, rat MCH has been characterised, and this prompted us to investigate the putative inhibitory activity of synthetic rat MCH on basal and stimulated ACTH secretion from freshly-dispersed rat pituitary cells or incubated rat pituitary fragments, as well on KCl (28 mmol/l) or noradrenaline-evoked release of corticotrophin releasing hormone-41 (CRH-41) from rat hypothalamic explants in vitro. There were no effects of rat MCH on either CRH-41 or ACTH release in vitro.

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Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells

Journal of Endocrinology ◽

10.1677/joe.0.1360381 ◽

1993 ◽

Vol 136 (3) ◽

pp. 381-387 ◽

Cited By ~ 40

Author(s):

A. E. Calogero ◽

G. Bagdy ◽

M. L. Moncada ◽

R. D'Agata

Keyword(s):

Receptor Antagonist ◽

Receptor Agonist ◽

Receptor Subtype ◽

Pituitary Cells ◽

Releasing Hormone ◽

Rat Pituitary ◽

Rat Pituitary Cells ◽

Level 2 ◽

Acth Release

ABSTRACT The present study was undertaken to evaluate the serotonin (5-HT) receptor subtype(s) by which 5-HT acts on the pituitary to stimulate ACTH secretion. We tested the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), the 5-HT1C receptor agonist metachloro-phenylpiperazine (m-CPP), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on basal, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP)-stimulated ACTH release from primary rat anterior pituitary cell cultures. 5-HT, 8-OH-DPAT and DOI significantly increased basal ACTH release, an effect which was antagonized by 5-HT receptor antagonists. 5-HT and DOI were effective at nanomolar concentrations whereas 8-OH-DPAT was effective at higher concentrations. 5-HT, 8-OH-DPAT (both at 10 nmol/l) and DOI (at higher concentrations) blunted the stimulatory effect of CRH. The suppressive effects of 8-OH-DPAT and DOI on CRH-stimulated ACTH release were antagonized by (−)propranolol, a β-adrenergic receptor antagonist which binds the 5-HT1A receptor with elevated affinity, and ketanserin, a 5-HT2 receptor antagonist respectively. 5-HT, 8-OH-DPAT and DOI showed additive stimulatory effects with AVP but only at the highest concentration tested, whereas m-CPP potentiated AVP-induced ACTH release at concentrations of 1 nmol/l or more. This effect was antagonized by metergoline, a non-selective 5-HT receptor antagonist and mianserin, an antagonist which binds the 5-HT1C receptor with elevated affinity. Thus (1) 5-HT and selective 5-HT agonists such as 8-OH-DPAT, m-CPP and DOI modulate ACTH release by acting directly at the pituitary level; (2) serotonergic stimulation of basal ACTH release is mediated by both 5-HT2 and 5-HT1A receptors; (3) serotonergic inhibition of CRH-stimulated ACTH release is mediated by 5-HT1A and 5-HT2 receptors; whereas (4) serotonergic potentiation of AVP-stimulated ACTH release is mediated mainly by 5-HT1C receptors. Journal of Endocrinology (1993) 136, 381–387

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