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.

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.

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).

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.