Pregnenolone 16-Alpha Carbonitrile, an Agonist of Rodent Pregnane X Receptor, Regulates Testosterone Biosynthesis in Rodent Leydig Cells.

Leydig cells (LCs) in the testes produce the male sex hormone testosterone (T). Several xenobiotics, including clinical drugs, supplements, and environmental chemicals, are known to disrupt T homeostasis. Notably, some of these xenobiotics are known to activate the pregnane X receptor (PXR), a ligand-dependent nuclear receptor.

Novel ectopic expression of zona pellucida 3 glycoprotein in lung cancer promotes tumor growth.

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown.

Current insight into the transient X-zone in the adrenal gland cortex.

Mouse models have been widely used in the study of adrenal gland development and diseases. The X-zone is a unique structure of the mouse adrenal gland and lineage-tracing studies show that the X-zone is a remnant of the fetal adrenal cortex. Although the X-zone is considered analogous to the fetal zone in the human adrenal cortex, the functional significance of the X-zone has remained comparatively more obscure.

Thyroid hormone-regulated chromatin landscape and transcriptional sensitivity of the pituitary gland.

Thyroid hormone (3,5,3'-triiodothyronine, T3) is a key regulator of pituitary gland function. The response to T3 is thought to hinge crucially on interactions of nuclear T3 receptors with enhancers but these sites in pituitary chromatin remain surprisingly obscure. Here, we investigate genome-wide receptor binding in mice using tagged endogenous thyroid hormone receptor β (TRβ) and analyze T3-regulated open chromatin using an anterior pituitary-specific Cre driver (Thrb).

DHCR24, a Key Enzyme of Cholesterol Synthesis, Serves as a Marker Gene of the Mouse Adrenal Gland Inner Cortex.

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by ).

Early transcriptomic response of mouse adrenal gland and Y-1 cells to dexamethasone.

Glucocorticoids have short- and long-term effects on adrenal gland function and development. RNA sequencing (RNA-seq) was performed to identify early transcriptomic responses to the synthetic glucocorticoid, dexamethasone (Dex), in vitro and in vivo. In total, 1711 genes were differentially expressed in the adrenal glands of the 1-h Dex-treated mice.

Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function.

The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans.

Isolate Cell-Type-Specific RNAs from Snap-Frozen Heterogeneous Tissue Samples without Cell Sorting.

Cellular heterogeneity poses challenges to understanding the function of complex tissues at a transcriptome level. Using cell-type-specific RNAs avoids potential pitfalls caused by the heterogeneity of tissues and unleashes the powerful transcriptome analysis. The protocol described here demonstrates how to use the Translating Ribosome Affinity Purification (TRAP) method to isolate ribosome-bound RNAs from a small amount of EGFP-expressing cells in a complex tissue without cell sorting.

A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice.

Background And Aim: Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is not well understood whether a combination therapy of DOX and CPS can induce hepatotoxicity.

Embryonic Steroids Control Developmental Programming of Energy Balance.

Glucose is a major energy source for growth. At birth, neonates must change their energy source from maternal supply to its own glucose production. The mechanism of this transition has not been clearly elucidated.

extract, at a physiologically relevant dosage, does not induce hepatotoxicity in C57BL/6J mice.

Background: Botanical supplements have been proven to provide beneficial health effects. However, they can induce unintended adverse events such as hepatotoxicity. extract (OIE, Sabroxy®) has several health benefits including anti-inflammatory, anti-arthritic, antifungal, antibacterial, and neuroprotective effects.

Expression of Rasd1 in mouse endocrine pituitary cells and its response to dexamethasone.

Dexamethasone-induced Ras-related protein 1 (Rasd1) is a member of the Ras superfamily of monomeric G proteins that have a regulatory function in signal transduction. Rasd1, also known as Dexras1 or AGS1, is rapidly induced by dexamethasone (Dex). While prior data indicates that Rasd1 is highly expressed in the pituitary and that the gene may function in regulation of corticotroph activity, its exact cellular localization in this tissue has not been delineated.

RNA-Seq Reveals Sub-Zones in Mouse Adrenal Zona Fasciculata and the Sexually Dimorphic Responses to Thyroid Hormone.

The sex-specific prevalence of adrenal diseases has been known for a long time. However, the reason for the high prevalence of these diseases in females is not completely understood. Mouse studies have shown that the adult adrenal gland is sexually dimorphic at different levels such as transcriptome, histology, and cell renewal.

Microwaving and Fluorophore-Tyramide for Multiplex Immunostaining on Mouse Adrenals - Using Unconjugated Primary Antibodies from the Same Host Species.

Immunostaining is widely used in biomedical research to show the cellular expression pattern of a given protein. Multiplex immunostaining allows labeling using multiple primary antibodies. To minimize antibody cross-reactivity, multiplex immunostaining using indirect staining requires unlabeled primary antibodies from different host species.

The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone.

The X-zone is a transient cortical region enriched in eosinophilic cells located in the cortical-medullary boundary of the mouse adrenal gland. Similar to the X-zone, the fetal zone in human adrenals is also a transient cortical compartment, comprising the majority of the human fetal adrenal gland. During adrenal development, fetal cortical cells are gradually replaced by newly formed adult cortical cells that develop into outer definitive zones.

A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1.

The development of the adrenal cortex involves the formation and then subsequent regression of immature or fetal inner cell layers as the mature steroidogenic outer layers expand. However, controls over this remodeling, especially in the immature inner layer, are incompletely understood. Here we identify an inner cortical cell population that expresses thyroid hormone receptor-β1 (TRβ1), one of two receptor isoforms encoded by the Thrb gene.

Investigating the role of adrenal cortex in organization and differentiation of the adrenal medulla in mice.

Functions of adrenal medulla, particularly synthesis of catecholamine, are under the control of glucocorticoids produced by the cortex. To further investigate whether development/differentiation of the adrenal medulla is associated with proper organization of the adrenal cortex, we examined development of the medulla in four different mouse models with various defects in the adrenal cortex. By using the Sf1/Cre mouse line that inactivates/activates genes in Steroidogenic factor 1 (SF1)-positive cells of the fetal adrenal cortex, we produced mice that exhibit either (1) cortex hypoplasia, (2) progressive degeneration of fetal adrenal cortex, (3) cortex dysgenesis, or (4) cortex-medulla disorganization.

Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for Dicer1 in adrenal, testis, and ovary.

Background: The synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking Dicer1 die in early embryogenesis.

Diverse functions of Hedgehog signaling in formation and physiology of steroidogenic organs.

Adrenal, testis, and ovary are steroidogenic organs derived from a common primordium that consists of steroidogenic factor 1 (SF1)-positive precursor cells. SF1 not only defines the steroidogenic lineages in these organs but also controls their differentiation. Recent evidence implicates the Hedgehog (Hh) signaling pathway as a downstream regulator of SF1 in the appearance of steroidogenic cells in these organs.

Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog.

The adrenal capsule is postulated to harbor stem/progenitor cells, the progenies of which contribute to the growth of adrenocortex. We discovered that cells in the adrenal capsule are positive for Ptch1 and Gli1, genes indicative of responsiveness to the stimulation of Hedgehog (Hh) ligands. On the other hand, Sonic hedgehog (Shh), one of the mammalian Hh ligands, is expressed in the adrenocortex underneath the adrenal capsule, possibly acting upon the Hh-Responsive capsule.

Mutation of mouse Cyp11a1 promoter caused tissue-specific reduction of gene expression and blunted stress response without affecting reproduction.

Steroids are synthesized mainly from the adrenal glands catalyzed by steroidogenic enzymes; the expression of these enzymes is controlled by transcription factor steroidogenic factor-1 (SF-1; NR5A1). To understand the physiological effect of genetic changes on steroid secretion, we used Cre-LoxP and gene targeting technology to mutate the binding sequence for SF-1 (SF-1 response element) on the promoter of the mouse Cyp11a1 gene, which encodes a critical enzyme for steroid biosynthesis. The resulting Cyp11a1 L/L mice expressed about 7-fold less cytochrome P450 side-chain cleavage enzyme (CYP11A1) in the adrenal and testis but expressed normal amounts of CYP11A1 in the placenta and ovary.

Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of steroidogenic factor 1 (NR5A1).

Histone deacetylase (HDAC) inhibitors such as trichostatin A and valproic acid modulate transcription of many genes by inhibiting the activities of HDACs, resulting in the remodeling of chromatin. Yet this effect is not universal for all genes. Here we show that HDAC inhibitors suppressed the expression of steroidogenic gene CYP11A1 and decreased steroid secretion by increasing the ubiquitination and degradation of SF-1, a factor important for the transcription of all steroidogenic genes.