Adipose tissue distribution in man is dependent on genetic and environmental factors. The total and regional masses of adipose tissue are dependent on the number of adipocytes as well as their degree of filling with depot fat. Currently available evidence does not suggest a specific regional regulation of fat cell multiplication in subcutaneous depots, which instead seems to occur at a certain critical degree of filling of available adipocytes. The control of the rate of filling of adipocytes then seems to be the main factor determining the local, regional mass of adipose tissue. This in turn is regulated by the balance between the lipid accumulating and mobilization processes. The steroid hormones exert major permissive effects on these processes. It seems likely that the resulting effect of the rate of secretion of various steroid hormones, and the local density of their specific receptors, decide the regional distribution of body fat. Physiological and clinical situations with defined differences in these regulatory factors would then be expected to have characteristically different adipose tissue distribution. Sex differences include a larger subcutaneous adipose tissue in women than men, explainable at least partly by a depot in the gluteal-femoral region in women, which is essentially absent in non-obese men. Men on the other hand seem to have a larger proportion of their adipose tissue organ localized intra-abdominally. In addition, the gluteal-femoral fat cells are specifically enlarged in women, and have a higher lipoprotein lipase activity. While the larger adipose tissue in non-obese women may well be genetically linked, the specific characteristics of the gluteal-femoral adipocytes are most likely regulated by female sex steroid hormones. Another apparent sex difference is the ability of women to protect visceral depots from fat accumulation up to a certain degree of obesity, while men deposit excess fat in this region in parallel with other depots. This might, at least partly, simply be explainable by the smaller 'available space' in male than female adipose tissue. It should be emphasized that the effects of sex steroid hormones on the regulation of adipocyte metabolism occur only in concert with cortisol, which is always present. Cortisol itself expresses lipoprotein lipase activity as well as beta-adrenergic receptors (BARs), and probably has additional effects, not yet revealed. The net effect seems, however, to be lipid accumulation as seen in the apparently glucocorticoid receptor (GR) dense visceral adipose tissue in conditions of glucocorticoid excess, such as Cushing's syndrome. The effects of the sex steroid hormones should be regarded against this background. A major difficulty in understanding the actions of female sex steroid hormones is the apparent lack of specific receptors in human adipose tissue. However, progesterone seems to compete over the GR, and may in this way 'protect' against cortisol effects. This might be the mechanism whereby young women do not accumulate visceral fat. Testosterone acts over a specific receptor, eliciting lipolytically active BARs, as well as inhibiting lipoprotein lipase activity. The high density of BAR activity in visceral fat in young men suggests specific regional effects also of testosterone on visceral adipose tissue, to diminish fat accumulation by a combination of lipoprotein lipase inhibition and BAR expression. This may be the mechanism whereby young men accumulate only small amounts of visceral fat, increasing with age and lower testosterone secretion. The interactions between cortisol on the one hand and progesterone or testosterone on the other would be expected to result in different net effects on the metabolic pathways for lipid accumulation and mobilization. In women progesterone might, via the GR, inhibit cortisol effects on lipoprotein lipase stimulation and presumably also inhibit lipolysis. In men testosterone might, via its own receptor, inhibit lipoprotein lipase activity and stimulate lipolysis. Lipoprotein lipase activity is not different in visceral fat in young men and women, while men have higher lipolysis. This then seems to fit with the mentioned hormonal interactions. Adipose redistribution following hormonal dysbalances between the pituitary-adrenal and pituitary-gonadal axes might be explained along similar lines. For example, with menopause and age the sex steroid protection of visceral depots disappears, and visceral fat accumulates. Preliminary intervention studies suggest that this can be prevented, supporting the suggested mechanisms of interaction. It is currently unclear, however, why hyperandrogenic syndromes in women are followed by visceral fat accumulation, and it is entirely possible that this working hypothesis for sex steroid hormone interactions in human adipose tissue regions needs a complete reevaluation when more information becomes available.
