scholarly journals Effects of ACTH (corticotropin) analogues on steroidogenesis and cyclic AMP in rat adrenocortical cells. Evidence for two different steroidogenically responsive receptors

1980 ◽  
Vol 186 (2) ◽  
pp. 599-603 ◽  
Author(s):  
A F Bristow ◽  
C Gleed ◽  
J L Fauchère ◽  
R Schwyzer ◽  
D Schulster

Comparative studies on the mechanism of action of ACTH1-39 and ACTH5-24 [corticotropin-(1-39)- and corticotropin-(5-24)-peptides] on isolated rat adrenal cells were performed. The relationship between stimulated steroidogenesis and cyclic AMP was very different, suggesting that cyclic AMP does not play the same role in mediating the action of the two agonists. Data from three separate experiments showed that the competitive antagonist ACTH6-24 [corticotropin-(6-24)-peptide] had mean inhibitor constants of 13.4 +/- 3.1 nM against ACTH1-39 and 3.4 +/- 1.0 nM against ACTH5-24, indicating that the steroidogenic actions of these two agonists are mediated by two different receptor types. We conclude that there are two possible mechanisms for corticotropin action, only one of which involves the necessary production of cyclic AMP.

1977 ◽  
Vol 72 (3) ◽  
pp. 757-763 ◽  
Author(s):  
A T Suyama ◽  
J A Long ◽  
J Ramachandran

The effects of ACTH, its o-nitrophenyl sulfenyl derivative (NPS-ACTH) and dibutyryl cyclic AMP (dbc AMP) on the ultrastructural morphology of adrenocortical cells of adult rats in monolayer culture have been investigated. NPS-ACTH, which has previously been shown to stimulate steroidogenesis but not cAMP synthesis in adrenal cells, induced the same characteristic transformation of mitochondrial architecture as produced by ACTH or high concentrations of dbcAMP. All three agents caused the disappearance of electron-opaque granules present in the mitochondria of unstimulated cells. It was found that these granules could be extracted with EGTA (ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetate). These results are discussed in the light of the known importance of calcium ions in the actions of ACTH.


Life Sciences ◽  
1982 ◽  
Vol 30 (25) ◽  
pp. 2235-2240 ◽  
Author(s):  
Kaname Moriwaki ◽  
Yoshiharu Itoh ◽  
Sayomi Iida ◽  
Kikuo Ichihara

1980 ◽  
Vol 186 (2) ◽  
pp. 391-397 ◽  
Author(s):  
Ernesto J. Podesta ◽  
Alfred Milani ◽  
Hans Steffen ◽  
Robert Neher

The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca2+. A rise in bound cyclic AMP with rising Ca2+ concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca2+-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca2+ has to be taken up in order to promote the rise of the relevant cyclic AMP pool. In agreement with this view, adenylate cyclase activity from isolated cells proved also to be dependent on a sub-millimolar Ca2+ concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca2+ in the absence of corticotropin (cells primed for Ca2+). Ca2+-induced steroidogenesis of these cells, in the absence of corticotropin, was also accompanied by an increase in total intracellular and receptor-bound cyclic AMP, as was found previously with corticotropin-induced steroidogenesis in non-primed cells. Calcium ionophores increasing the cell uptake of Ca2+ were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca2+ in cells primed for Ca2+. It was concluded that during stimulation by either corticotropin or Ca2+ a possible cellular uptake of Ca2+ must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor–adenylate cyclase complex.


1984 ◽  
Vol 106 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Jan Sogn ◽  
Gun Abrahamsson ◽  
Per O. Janson

Abstract. A model for in vitro perfusion of the isolated rat ovary was developed. In the luteinized ovaries of PMSG treated rats the relationship between perfusion flow and progesterone production was evaluated. A positive correlation was found indicating that a high blood flow rate may be necessary for an optimal secretion of progesterone from the fully developed corpus luteum in the rat. Also the effects of a continuous exposure of LH on ovarian cyclic AMP and progesterone release was studied. A rapid and sustained increase in both cyclic AMP and progesterone release was seen and this release tended to have episodic pattern with elevations occurring at intervals between 30 and 90 min following LH.


1979 ◽  
Vol 82 (2) ◽  
pp. 275-277 ◽  
Author(s):  
T. HIROSE ◽  
I. MATSUMOTO ◽  
T. AIKAWA

SUMMARY The steroidogenic effect of histamine in isolated adrenocortical cells of the dog was investigated in the presence of prostaglandin E2 (PGE2) and/or dibutyryl cyclic AMP (dbcAMP) in the medium. The effect of histamine, in combination with PGE2, was less than their total individual effects in the production of cortisol, but not of corticosterone. With dbcAMP the effect was just equal to them. However, the combination of histamine, PGE2 and dbcAMP showed an increase twice that of their total individual effects in the production of both steroids. These results indicate that, in the dog, histamine, PGE2 and dbcAMP may act synergistically in the adrenocortical cells.


1974 ◽  
Vol 142 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Kenneth Siddle ◽  
C. Nicholas Hales

The relationship between cyclic AMP content and lipolysis, as measured by glycerol formation, was studied in isolated rat fat-cells. Inhibition of lipolysis by insulin in the presence of a low concentration of adrenaline was accompanied by little or no lowering of cyclic AMP content, measured after 15min incubation. The time-course of cyclic AMP content after addition of adrenaline showed that the effect of insulin in lowering cyclic AMP content measured after 2–5min was gradually lost over the next hour, mainly because of the fall in cyclic AMP content after an early peak in the presence of adrenaline alone. There was a 44% loss of immunoreactive insulin, from an initial concentration of 0.3nm, during a 1h incubation with fat-cells. Insulin did not affect partitioning of cyclic AMP between cells and incubation medium. When the correlation between cyclic AMP content and rate of lipolysis was investigated for a wide range of adrenaline concentrations, it was found that the lowering of cyclic AMP content by insulin was much less than that required to account for the amount of inhibition of lipolysis. It is concluded that inhibition of adrenaline-stimulated lipolysis by insulin involves factors in addition to a decrease in intracellular cyclic AMP concentration.


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