All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause.

The Journal of steroid biochemistry and molecular biology (2014-06-14)
Fernand Labrie
RESUMEN

Following the arrest of estradiol secretion by the ovaries at menopause, all estrogens and all androgens in postmenopausal women are made locally in peripheral target tissues according to the physiological mechanisms of intracrinology. The locally made sex steroids exert their action and are inactivated intracellularly without biologically significant release of the active sex steroids in the circulation. The level of expression of the steroid-forming and steroid-inactivating enzymes is specific to each cell type in each tissue, thus permitting to each cell/tissue to synthesize a small amount of androgens and/or estrogens in order to meet the local physiological needs without affecting the other tissues of the organism. Achieved after 500 million years of evolution, combination of the arrest of ovarian estrogen secretion, the availability of high circulating levels of DHEA and the expression of the peripheral sex steroid-forming enzymes have permitted the appearance of menopause with a continuing access to intratissular sex steroids for the individual cells/tissues without systemic exposure to circulating estradiol. In fact, one essential condition of menopause is to maintain serum estradiol at biologically inactive (substhreshold) concentrations, thus avoiding stimulation of the endometrium and risk of endometrial cancer. Measurement of the low levels of serum estrogens and androgens in postmenopausal women absolutely requires the use of MS/MS-based technology in order to obtain reliable accurate, specific and precise assays. While the activity of the series of steroidogenic enzymes can vary, the serum levels of DHEA show large individual variations going from barely detectable to practically normal "premenopausal" values, thus explaining the absence of menopausal symptoms in about 25% of women. It should be added that the intracrine system has no feedback elements to adjust the serum levels of DHEA, thus meaning that women with low DHEA activity will not be improved without external supplementation. Exogenous DHEA, however, follows the same intracrine rules as described for endogenous DHEA, thus maintaining serum estrogen levels at substhreshold or biologically inactive concentrations. Such blood concentrations are not different from those observed in normal postmenopausal women having high serum DHEA concentrations. Androgens, on the other hand, are practically all made intracellularly from DHEA by the mechanisms of intracrinology and are always maintained at very low levels in the blood in both pre- and postmenopausal women. Proof of the importance of intracrinology is also provided, among others, by the well-recognized benefits of aromatase inhibitors and antiestrogens used successfully for the treatment of breast cancer in postmenopausal women where all estrogens are made locally. Each medical indication for the use of DHEA, however, requires clinical trials performed according to the FDA guidelines and the best rules of clinical medicine.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone solution, 50 μM, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Progesterone, ≥99%
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Supelco
Dehydroepiandrosterone (DHEA) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Cortisol solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Progesterone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
trans-Dehydroandrosterone, ≥99%
Hydrocortisone, European Pharmacopoeia (EP) Reference Standard
Supelco
Progesterone solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, meets USP testing specifications
USP
Hydrocortisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Hydrocortisone for peak identification, European Pharmacopoeia (EP) Reference Standard
USP
Progesterone, United States Pharmacopeia (USP) Reference Standard
Supelco
Progesterone, VETRANAL®, analytical standard
Supelco
Hydrocortisone, VETRANAL®, analytical standard
Progesterone, European Pharmacopoeia (EP) Reference Standard