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A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ER α expressing primary and metastatic invasive ductal carcinoma
In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.
Source: Frontiers in Endocrinology - April 18, 2023 Category: Endocrinology Source Type: research

MicroRNA-574 Impacts Granulosa Cell Estradiol Production via Targeting TIMP3 and ERK1/2 Signaling Pathway
Estradiol represents a key steroid ovarian hormone that not only plays a vital role in ovarian follicular development but also is associated with many other reproductive functions. Our primary study revealed that miR-574 expression decreased in porcine granulosa cells during development from small to large follicles, and the increase of ERK1/2 phosphorylation accompanies this change. Since it has been well established that the ERK1/2 activity is tightly associated with granulosa cell functions, including ovarian hormone production, we thus further investigate if the miRNA is involved in the regulation of estradiol product...
Source: Frontiers in Endocrinology - June 23, 2022 Category: Endocrinology Source Type: research

Role of the Ubiquitin Ligase RNF149 in the Development of Rat Neonatal Gonocytes
Male reproductive function depends on the formation of spermatogonial stem cells from their neonatal precursors, the gonocytes. Previously, we identified several UPS enzymes dynamically altered during gonocyte differentiation. The present work focuses on understanding the role of the RING finger protein 149 (RNF149), an E3 ligase that we found to be strongly expressed in gonocytes and downregulated in spermatogonia. The quantification of RNF149 mRNA from postnatal day (PND) 2 to 35 (puberty) in rat testis, brain, liver, kidney, and heart indicated that its highest levels are found in the testis. RNF149 knock-down in PND3 r...
Source: Frontiers in Endocrinology - May 13, 2022 Category: Endocrinology Source Type: research

The multifaceted biology of PCSK9
This article reviews the discovery of PCSK9, its structure-function characteristics, and its presently known and proposed novel biological functions. The major critical function of PCSK9 deduced from human and mouse studies, as well as cellular and structural analyses, is its role in increasing the levels of circulating LDL-cholesterol (LDLc), via its ability to enhance the sorting and escort of the cell surface LDL receptor (LDLR) to lysosomes. This implicates the binding of the catalytic domain of PCSK9 to the EGF-A domain of the LDLR. This also requires the presence of the C-terminal Cys/His-rich domain (CHRD), its bind...
Source: Endocrine Reviews - October 9, 2021 Category: Endocrinology Authors: Nabil G Seidah Annik Prat Source Type: research

Bitter taste signaling mediated by Tas2r144 is down-regulated by 17β-estradiol and progesterone in the rat choroid plexus
Publication date: Available online 25 July 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Joana Tomás, Cecília R.A. Santos, Ana C. Duarte, Maria Maltez, Telma Quintela, Manuel C. Lemos, Isabel GonçalvesAbstractThe blood-cerebrospinal fluid barrier is constituted by choroid plexus epithelial cells (CPEC) that regulate molecular trafficking between the blood and the cerebrospinal fluid. We hypothesize that taste receptors expressed in CPEC monitor the composition of these body fluids in a sex hormone dependent way. Thus, we compared the expression of taste related genes in the choroid plexus of sham and ovarie...
Source: Molecular and Cellular Endocrinology - July 26, 2019 Category: Endocrinology Source Type: research

Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells.
Authors: Nagao S, Iwata N, Soejima Y, Takiguchi T, Aokage T, Kozato Y, Nakano Y, Nada T, Hasegawa T, Otsuka F Abstract A functional link between clock gene expression and ovarian steroidogenesis was studied using human granulosa KGN cells. Similarities between changes in the mRNA and protein expression levels of Bmal1 and Clock and those of Per2 and Cry1 were found in KGN cells after treatment with forskolin. Among the interrelationships between the expression levels of clock and steroidogenic factors, Clock mRNA had a strongly positive correlation with P450arom and a negative correlation with 3βHSD. Knockdown of ...
Source: Endocrine Journal - December 8, 2018 Category: Endocrinology Tags: Endocr J Source Type: research

Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation
In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Wes...
Source: Molecular and Cellular Endocrinology - July 10, 2018 Category: Endocrinology Source Type: research

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