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The risk of developing PC seems to be related to the diet

In the human prostate, ERβ is expressed in the basal epithelial cells and AR in the luminal epithelium.

For many years, DHT was considered to be the main hormone guiding prostate development and function. However, the idea was challenged when in 2001 Mahendroo et al. showed that mice in which both forms of 5α-reductase had been inactivated, have a normal functional prostate [50]. The question was then raised as to what is the real function of DHT in the prostate. In 1989 we hypothesized that DHT is a precursor of an oestrogen, 5α-androstane-3β,17β-diol (3β-Adiol) and that physiological levels of an oestrogen could be produced in the total absence of aromatase [51]. We later demonstrated that 3β-Adiol is abundant in the prostate and is a good natural ligand for ERβ

The overall effect of oestrogens in the immune system is determined by a balance between ERα and ERβ signalling

The hypothesis of our group is that ERβ plays an important role in regulating the differentiation of pluripotent haematopoietic progenitor cells whereas ERα induces proliferation

In tissues and cell lines of mammary epithelium for example, it has been noticed that E2 in the presence of ERα elicits proliferation, but in the presence of ERβ it inhibits proliferation

ERα and ERβ have distinctive tissue distributions and to the great surprise of endocrinologists [7] many tissues previously thought to be ‘oestrogen-insensitive tissues’ were found to be ERβ positive and oestrogen sensitive. The most notable of the ERα-negative ERβ-abundant tissues were the epithelium of the rodent ventral prostate [8], the granulosa cells of the ovaries [9] and the parenchyma of the lungs

Leptin is a potent anorexigenic and catabolic hormone secreted by adipose cells that reduces food intake and increases energy expenditure

E2 not only modulates leptin receptor mRNA in the ARC and VMH, but also increases hypothalamic sensitivity to leptin, altering peripheral fat distribution

ghrelin. It acts on growth hormone secretagogue receptors (GHSR1a) located in the ARC and is a potent stimulator of food intake

It thus appears that of the two ERs, ERα plays a predominant role in the CNS regulation of lipid and carbohydrate homeostasis.

Both ERs have been identified in the ARC

Stimulation of MCH neurons increases food intake and fat accumulation while its inhibition leads to decreased food intake and reduced fat accumulation.

Both ERs have been identified in the LH

both ERs have been identified in this nucleus

The PVN is the region of the hypothalamus with the highest expression of ERβ and is reported to be weakly ERα positive

The VMH is ERα regulated

Skeletal muscle is responsible for 75% of the insulin-induced glucose uptake in the body

GLUT4 is highly expressed in muscle and represents a rate-limiting step in the insulin-induced glucose uptake

data suggest that in the physiological range, E2 is beneficial for insulin sensitivity, whereas hypo- or hyperestrogenism is related to insulin resistance

In aging female rats, E2 treatment improves glucose homeostasis mainly through its ability to increase muscle GLUT4 content on the cell membrane

It is evident that ERα and ERβ have distinct actions and that much more research is needed to clearly identify the function of each receptor in muscle.

E2 prevents accumulation of visceral fat, increases central sensitivity to leptin, increases the expression of insulin receptors in adipocytes, and decreases the lipogenic activity of lipoprotein lipase in adipose tissue

In rats, ovariectomy increases body weight, intra-abdominal fat, fasting glucose and insulin levels, and insulin resistance followed by decreased phosphorylation of AMPK and its substrate acetyl-CoA carboxylase in adipose tissue

decreased adiponectin, PPARγ coactivator-1α (PGC-1α), and uncoupling protein 2 (UCP2) and increased resistin

Men with aromatase deficiency have truncal obesity, elevated blood lipids, and severe insulin resistance

Although not all studies are in agreement, polymorphisms of ERα in humans have been associated with risk factors for CVDs

Human subcutaneous and visceral adipose tissues express both ERα and ERβ, whereas only ERα mRNA has been identified in brown adipose tissue

suggesting that ERα is the main regulator of GLUT4 expression in adipose tissue