Nestorone , a 19nor-progesterone derivative boosts remyelination in an animal model of demyelination.

Introduction: We previously showed that Nestorone (NES), a synthetic progestin structurally related to progesterone, stimulated remyelination of the corpus callosum in a Cuprizone (CUP) mouse model of demyelination in intact females by promoting replenishment with mature oligodendrocytes (OL) (Glia. 2015;63:104-117). Here, we further investigated the underlying mechanisms of this promyelinating effect.

The progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in the wobbler mouse model of motoneuron degeneration.

Wobbler mutant mice suffer from progressive motoneuron degeneration and glial cell reactivity in the spinal cord. To prevent development of these abnormalities, we employed Nestorone, a high-affinity progesterone receptor agonist endowed with neuroprotective, promyelinating and anti-inflammatory activities in experimental brain ischemia, preventing neuroinflammation and chemical degeneration. Five-month-old Wobbler mice (wr-/wr-) received s.

Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors.

Progesterone is commonly considered as a female reproductive hormone and is well-known for its role in pregnancy. It is less well appreciated that progesterone and its metabolite allopregnanolone are also male hormones, as they are produced in both sexes by the adrenal glands. In addition, they are synthesized within the nervous system.

Progesterone and related progestins: potential new health benefits.

Progesterone is a steroid hormone that is essential for the regulation of reproductive function. The main physiological roles of this hormone have been widely described. Progesterone and progestins have been approved for a number of indications including the treatment of irregular and anovulatory menstrual cycles and, when combined with estrogen, for contraception, and the prevention of endometrial hyperplasia in postmenopausal hormonal replacement therapy (HRT) regimens.

Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills.

Estrogen and progestins have been used by millions of women as effective combined oral contraceptives. Oral contraceptives (OCs) modify surrogate markers such as lipoproteins, insulin response to glucose, and coagulation factors, that have been associated with cardiovascular and venous risk. Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism.

The use of newer progestins for contraception.

The synthetic progestins used for contraception so far are structurally related either to testosterone (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor (GR) interactions. Dienogest (DNG) and drospirenone (DRSP) exhibit a partial antiandrogenic action, and DRSP has predominant anti-mineralocorticoid properties.

New hormonal therapies and regimens in the postmenopause: routes of administration and timing of initiation.

Since the publication of the Women's Health Initiative (WHI) study followed by the results of the Million Women Study (MWS), the role of hormonal therapy in postmenopausal women has been further challenged. The risks attributed to hormone therapy have been overestimated and the data has been wrongly extrapolated to the whole class of therapies. The trends in postmenopausal hormonal therapy seem now to favor the non-oral delivery routes for both the estrogen and the progestin for women with an intact uterus, based on the assumption that a lesser stimulation of the liver proteins and a neutral metabolic profile would be more favorable in terms of cardiovascular and venous risk.

Protein kinase C increases 11beta-hydroxysteroid dehydrogenase oxidation and inhibits reduction in rat Leydig cells.

Glucocorticoid hormone controls Leydig cell steroidogenic function through a receptor-mediated mechanism. The enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD) plays an important role in Leydig cells by metabolizing glucocorticoids, and catalyzing the interconversion of corticosterone (the active form in rodents) and 11-dehydrocorticosterone (the biologically inert form). The net direction of this interconversion determines the amount of biologically active ligand, corticosterone, available for glucocorticoid receptor binding.

Müllerian inhibiting substance inhibits testosterone synthesis in adult rats.

Müllerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS.

Identification and implantation stage-specific expression of an interferon-alpha-regulated gene in human and rat endometrium.

Implantation of the developing blastocyst is regulated by multiple effectors, such as steroid hormones, growth factors, and cytokines. To understand how these diverse signaling pathways interact to modulate uterine gene expression, we employed a gene expression screen technique to identify the molecules that are induced in the periimplantation rat uterus. Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1).

Initial predominance of the oxidative activity of type I 11beta-hydroxysteroid dehydrogenase in primary rat Leydig cells and transfected cell lines.

Glucocorticoids suppress testosterone production in Leydig cells. The level of glucocorticoid action is set within the Leydig cell by the number of glucocorticoid receptors and by the activity of 11beta-hydroxysteroid dehydrogenase (11betaHSD). This enzyme acts either as an oxidase inactivating glucocorticoid or as a reductase amplifying its action.

Cloning and uterus/oviduct-specific expression of a novel estrogen-regulated gene (ERG1).

The steroid hormone estrogen profoundly influences growth and differentiation programs in the reproductive tract of cycling and pregnant mamals. It is thought that estrogen exerts its cellular effects by regulating the expression of specific target genes. We utilized a messenger RNA differential display method to identify the genes whose expression is modulated by estrogen in the preimplantation rat uterus.

Opposing changes in 3alpha-hydroxysteroid dehydrogenase oxidative and reductive activities in rat leydig cells during pubertal development.

The enzyme 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) has an important role in androgen metabolism, catalyzing the interconversion of dihydrotestosterone (DHT) and 5alpha-androstane-3alpha,17beta-diol (3alpha-DIOL). The net direction of this interconversion will affect the amount of biologically active ligand available for androgen receptor binding. We hypothesize that in Leydig cells, differential expression of 3alpha-HSD enzymes favoring one of the two directions is a mechanism by which DHT levels are controlled.

Variation in the end products of androgen biosynthesis and metabolism during postnatal differentiation of rat Leydig cells.

The amount of testosterone (T) secreted by Leydig cells is determined by a balance between T biosynthetic and metabolizing enzyme activities. It has been established that 5alpha-androstan-3alpha,17beta-diol (3alpha-DIOL) is the predominant androgen secreted by the testes of immature rats during days 20-40 postpartum, whereas T is the major androgen by day 56. However, the underlying changes in T biosynthetic and metabolizing enzymes during Leydig cell development and their magnitudes have remained unclear.

Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation.

The peptide hormone calcitonin plays a key role in calcium homeostasis in many tissues, such as bone and kidney. Our previous studies revealed that the expression of calcitonin is dramatically induced in the glandular epithelium of rat uterus between days 3-5 of pregnancy before the onset of blastocyst implantation on day 5. Calcitonin expression is switched off once implantation has progressed to day 6.

Developmental changes in glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase oxidative and reductive activities in rat Leydig cells.

Glucocorticoids directly regulate testosterone production in Leydig cells through a glucocorticoid receptor (GR)-mediated repression of the genes that encode testosterone biosynthetic enzymes. The extent of this action is determined by the numbers of GR within the Leydig cell, the intracellular concentration of glucocorticoid, and 11beta-hydroxysteroid dehydrogenase (11betaHSD) activities that interconvert corticosterone (in the rat) and its biologically inert derivative, 11-dehydrocorticosterone. As glucocorticoid levels remain stable during pubertal development, GR numbers and 11betaHSD activities are the primary determinants of glucocorticoid action.