Search Results

Institut de Physiologie, ERA 412 CNRS, 2 rue F. Magendie, 31400 Toulouse, France

(Received 20 January 1978)

It has never been clearly shown that endogenous corticotrophin (ACTH) affects the release of storage fat. Desbals, Desbals & Agid (1970) observed significant mobilization of lipid within a few hours of ablation of the adrenal glands in the rabbit; this response was prevented by hypophysectomy and could be restored by administration of ACTH. A possible extra-adrenal action of endogenous ACTH on adipose tissue was postulated from these results, but the experimental conditions were very different from those found in normal animals. This study was undertaken to investigate the physiological role of ACTH in the mobilization of fat in the rabbit. The rabbit was selected because of the extreme sensitivity of its adipose tissue to the lipolytic action of ACTH and its very slight responsiveness towards the lipolytic action of catecholamines in vivo (Desbals

The effect of minor stressful stimuli (saline infusions or venepunctures) on lipid mobilization (estimated by plasma free fatty acids (FFA) and glycerol levels) was studied in two strains of conscious rabbits of various ages. Infusions of 0·9% (w/v) NaCl solution induced a prompt increase of FFA levels in naturally obese rabbits while this effect was absent in younger lighter animals. Administration of propranolol (a β-adrenoceptor blocking drug) beforehand did not prevent lipid mobilization. Adipose tissue in vitro was completely unresponsive to the lipid mobilizing action of adrenaline. The initial output of ACTH induced by stressful stimuli was quickly followed by the increase in the plasma concentration of FFA. A highly significant correlation (r = 0·84 or 0·85; P< 0·01) existed between plasma ACTH and FFA levels 30 and 60 min after the start of stress. Dexamethasone completely prevented lipid mobilization while adipose tissue in vivo and in vitro responded strongly to ACTH. Consequently the lack of response of plasma FFA concentrations in corticosteroid-treated rabbits seemed to be linked to the failure of the pituitary gland to mobilize ACTH rather than to the unresponsiveness of adipose tissue to the pituitary hormone.

Our data indicate that in the rabbit, under conditions of stress, ACTH is of greater physiological importance than catecholamines in the control of lipolysis.

ABSTRACT

The adrenergic antagonists [³H]prazosin and [³H] rauwolscine were used to identify α₁- and α₂-adrenoceptors respectively in the ovine myometrium. Ewes were allocated to four groups according to steroid hormone treatments or physiological status, namely ovariectomized ewes either as untreated controls, treated with oestradiol-17β or progestagen plus oestradiol-17β, and pregnant ewes at mid-gestation. Binding of both [³H]prazosin and [³H]rauwolscine to membrane preparations from the ovine myometrium was saturable, of high affinity and rapidly reversed by phentolamine (10 μmol/l). Based on the relative order of potency of selected adrenergic agonists and antagonists, the myometrial binding sites labelled by [³H]prazosin and [³H]rauwolscine were characterized as α₁- and α₂adrenoceptors respectively. Saturation binding studies with [³H]prazosin showed that the number of α₁adrenoceptors was low (maximal binding capacity, B_max, between 19 and 24 fmol/mg protein) and there were no noticeable differences between the animal groups. Moreover, the equilibrium dissociation constant (K _d) did not vary significantly between groups (K _d between 0·10 and 0·17 nmol/l). In contrast, saturation binding studies with [³H]rauwolscine revealed the presence of a high number of α₂-adrenoceptors. Values of B_max were far higher in the pregnant ewes (1096±241 fmol/mg protein; means ± s.d.) than in any of the non-pregnant ovariectomized ewes. For these latter groups, the highest B_max values were found in the group treated with both progestagen and oestrogen (382±77 fmol/mg protein) compared with treatment with oestrogen alone (101±8 fmol/mg protein) or with controls (82±12 fmol/mg protein). The results of the present study, especially those obtained under a high-progesterone environment (e.g. pregnancy), strongly suggest a role of steroid hormones in the control of the number of α₂-adrenoceptors in the ovine myometrium. In contrast, they did not yield any supporting data for a similar role on myometrial α₁-adrenoceptors in the ewe.

Journal of Endocrinology (1990) 127, 471–479