Estrogen receptor transcription and transactivation: Basic aspects of estrogen action

Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERβ, was reported. An intricate interplay between the classical ERα and the novel ERβ is of paramount importance for the final biological effect of estrogen in different target cells.     

Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study

Background  

The estrogen receptors α and β (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes.     

Estrogen action in mood and neurodegenerative disorders

In this review, estrogenic effects in depression, anxiety, and neurodegenerative disorders are summarized. Moreover, preclinical findings from in vitro and animal models are discussed. There is a correlation between decreased estrogen levels (e.g., premenstrually, during the postpartum period, and perimenopausally) and increased anxiety and depressive symptoms. Several studies show beneficial effects of estrogen treatment in women with anxiety and depressive symptoms. Recent data indicate that the estrogen receptor (ER) β appears to be a major mediator of estrogenic effects in depression and anxiety. Additionally, both preclinical and clinical findings suggest that activation of estrogen receptors have an important role in neuroprotective and neurodegenerative processes in the mammalian central nervous system (CNS).     

Effects of some common inducers on the hepatic microsomal metabolism of androstenedione in rainbow trout with special reference to cytochrome P-450-dependent enzymes

The effects of 16α-cyanopregnenolone, 3-methylcholanthrene (3-MC), Clophen A 50 (Cl 50) and phenobarbital on the total amount of cytochrome P-450 and the metabolism of 4-androstene-3,17-dione in liver microsomes from rainbow trout were studied. Only 3-MC and CI 50 caused marked changes in the cytochrome P-450 levels and the cytochrome P-450-dependent steroid hydroxylase activities. A varying response to 3-MC and Cl 50 was seen in fish of different ages and sex. Different responses of 6β-hydroxylase towards α-naphtoflavone, SKF 525-A and metyrapone in vitro were seen in 3-MC- and Cl 50-treated fish when compared to control fish. It is suggested that endocrine factors may be involved in the regulation of cytochrome P-450-mediated metabolism in fish and the presence of multiple forms of cytochrome P-450 in trout liver is indicated.     

Biotransformation of benzo[a]pyrene and 7-ethoxyresorufin and heme-staining proteins in microsomes from human fetal liver and placenta

Microsomal proteins from human fetal livers and mid-gestational and term placentas were stained for heme in an attempt to detect multiple forms of cytochrome P-450. In fetal liver microsomes five protein bands staining for heme in the mol. wt region 46,000-60,000 were found. In the placentas two bands were seen in the region 46,000-52,000. Fetal liver and placental microsomes were assayed for metabolism of benzo[a]pyrene (B[a]P and 7-ethoxyresorufin (7-EOR). The B[a]P metabolites were separated using high performance liquid chromatography. Following incubations with fetal liver microsomes, in general only phenols were detectable, while after incubations with mid-gestational as well as term placentas from smoking women, the 9,10-, 4,5- and 7,8-dihydrodiols were also formed. No quinones were detected. Placental microsomes from non-smoking women did not catalyse the formation of B[a]P metabolites. The 7-EOR O-de-ethylase activity was in the same range (2-5 pmol/min x mg microsomal protein) in the fetal livers as in the mid-gestational placentas. The activities were somewhat higher in the placentas originating from smokers. No correlation between enzymatic activities in vitro and intensity of any specific protein band was observed for the fetal livers of placentas studied.     

The effects on hepatic steroid metabolism of an ectopic pituitary graft: A time study

The time course of feminization of hepatic steroid metabolism in the rat was followed after transplantation of a normal male or female pituitary gland under the kidney capsule of the host animal. Feminization of enzymes active on 4-androstene-3,17-dione and 5α-androstane-3α, 17β-diol occurred between 4 and 8 days after transplantation. Prior to this, masculinization of liver enzyme activities was seen in the transplanted animals. The data on concentrations of lutropin (LH), follitropin (FSH) and prolactin in host serum indicated that, of these hormones, only prolactin was produced by the ectopic pituitary gland. A lag period of 2–4 days was observed before prolactin appeared in host serum. The serum concentrations of prolactin, lutropin and follitropin were poorly correlated with the degree of feminization of hepatic steroid metabolism in the host animal. It thus appears that the ectopic pituitary gland within 4–8 days after implantation begins to secrete (a) factor(s) which is (are) not identical to prolactin, lutropin or follitropin, and which feminize(s) the steroid metabolism in the liver.     

The effect of 2-Br-α-ergocryptine on the hepatic steroid metabolism and serum pituitary hormone levels in normal rats and rats with an ectopic pituitary

The effect of a dopaminergic agonist, CB-154 (2-Br-α-ergocryptine), on the hepatic steroid metabolism in normal male and female rats, and in hypophysectomized male animals bearing an implanted pituitary under the kidney capsule, has been investigated. The serum levels of the four pituitary hormones LH, FSH, prolactin and growth hormone, were also measured. In normal animals, CB-154 reduced the serum level of prolactin without significantly affecting levels of LH, FSH or growth hormone and without masculinizing hepatic steroid metabolism of female rats of feminizing hepatic steroid metabolism of male rats. Implantation of a pituitary gland from age-matched female rats in hypophysectomized male rats caused an increase in prolactin and growth hormone levels in serum and a shift towards a more feminine type of steroid metabolism. Treatment with CB-154 reduced the prolactin level without affecting LH, FSH or growth hormone levels and without masculinizing hepatic steroid metabolism. In conclusion, the drug, CB-154, causes a marked and selective decrease in circulating prolactin levels without affecting the sex differentiation of hepatic steroid metabolism thus indicating that these two parameters are not related. A certain correlation between growth hormone levels and degree of femininity of steroid metabolism was seen but the significance of this is debatable.