Testosterone treatment of ovariectomized rats: Effects on lipolysis regulation in adipocytes

Abstract

The effects of testosterone treatment (2 mg every 14 days, for three months) on adipocyte lipolysis of intact (250-300 g body weight) and ovariectomized female rats were studied. Testosterone treatment of intact rats had no effect. Ovariectomy was followed by an increase in fat cell size and a decrease of lipolysis stimulated by isoproterenol, norepinephrine, epinephrine, forskolin, cAMP and isobutylmethylxantine. The number of \ g=b\ -adrenergic receptors was reduced. There was, however, no change in the antilipolytic effects of UK 14,304 (alpha2-adrenergic agonist), nicotinic acid, N -phenylisopropyladenosine or insulin. Testosterone treatment of ovariectomized rats restored the number of \g=b\-adrenoceptors and lipolysis stimulated by cAMP and isobutylmethylxantine, but not lipolysis stimulated by catecholamines and forskolin, suggesting a remaining defect in the catalytic unit of adenylate cyclase. These results indicate that ovariectomy is followed by a profound derangement of the lipolytic pathway at several levels, from \g=b\-adrenoceptors number to the triglyceride lipase activity. This is partially restored by treatment with testosterone, which, however, has no effect on intact female rats. This study emphasizes the importance of ovarian integrity for the lipolytic regulation and the inability of testosterone to replace ovarian function in this regard or to affect lipolysis in intact female rats.Sex steroid hormones influence adipose tissue me¬ tabolism and body fat mass through activation of specific intracellular receptors in adipocytes (1-4). Several studies have investigated the separate or combined effects of estrogen and progesterone on lipoprotein lipase activity (5-13), but only few reports have focused on the effects of these hor¬ mones on lipolysis. In female rats, estrogen treat¬ ment increases the lipolytic responsiveness to catecholamines and progesterone has no effect on the glycerol release (13-15); in male adipose precursor cells, testosterone enhances the lipolytic capacity of these cells by increasing the apparent number of ß-adrenoceptors and the activity of adenylate cyclase (3).It is now well established that accumulation of intra-abdominal fat in humans is closely associated with higher cardiovascular risk and disturbances in carbohydrate and lipid metabolism (16)(17)(18)(19); more¬ over, premenopausal women with abdominal obe¬ sity are characterized by increased androgenic ac¬ tivity (20-21) and more lipolytic abdominal adi¬ pocytes than women with gluteal-femoral obesity (22). Thus, androgens seem to be involved in these effects.Since the effects of androgens on lipolysis are relatively little known in the female sex, we decided to examine this aspect by treating ovariectomized and intact female rats with testosterone. Materials and Methods Chemicals[125]cyanopindolol (2220 Ci/mmol) was from the Radiochemical Centre (Amersham, UK). Collagenase type I, bovine serum albumin, forskolin, isoproterenol bitartrate, epinephrine bitartrate, norepinephrine bitartrate,

Effects of hindlimb suspension and androgen treatment on testosterone receptors in rat skeletal muscles

“…Conversely, when plasma testosterone concentrations increased after anabolic steroid administration, B max decreased and K d increased. This result was in agreement with previous results which have shown that the testosterone status aects B max and af®nity of testosterone receptors (Saartok et al 1984;De Pergola et al 1990). It has been shown before in rats that before maturity, B max values were elevated whereas plasma testosterone concentrations were very low.…”

“…This ®nding has been partly explained by a decrease in the androgen receptor concentration related to steroid administration (Hickson et al 1983;De Pergola et al 1990). The androgen receptor concentration in skeletal muscle depends on various factors, such as the ®bre-type composition, concentration of plasma testosterone, and contractile activity.…”

Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots

“…Unfortunately, the experiments on omental cells of men were too few Our results for testosterone and lipolysis are different from those reported in several rodent studies. In rodents, testosterone up-regulates catecholamine-induced lipolysis when investigated in vivo or in vitro using mature fat cells or differentiated pre-adipocytes [21,22,23]. This difference between results for humans and for rodents suggests that there are important species differences in the effect of testosterone on lipolysis.…”

Relation between sex hormones and serum lipoprotein and lipoprotein(a) concentrations in premenopausal obese women.

“…23 " 28 It is noteworthy that in abdominal adipocytes, testosterone promotes cell enlargement and enhances the lipolytic response to catecholamines. 29 " 31 Since most of the perivisceral abdominal fat is drained by the portal vein, 32 an increase of circulating free testosterone, as has been described in obese women with abdominal fat accumulation, 2633 may result in elevated portal free fatty acid concentrations that in turn may alter the metabolism of lipoproteins in the liver. 34 Interestingly, no information is available about the prevalence of high Lp(a) levels in obese women as well as about the possible adverse effects of androgens on Lp(a) levels in women.…”