Molecular aspects of the ontogeny of the pituitary-gonadal axis

1995 ◽  
Vol 7 (5) ◽  
pp. 1025 ◽  
Author(s):  
I Huhtaniemi
Keyword(s):  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Feedback Regulation ◽  
Reproductive Organs ◽  
Endocrine Function ◽  
Male Rat ◽  
Fetal Life ◽  
Hormone Production ◽  
Endocrine Activity ◽  
Hormonal Stimulus

The endocrine function of the mammalian pituitary-gonadal axis begins in utero. This is important particularly for the ontogeny and function of the male reproductive organs, the induction of which is critically dependent on the two fetal testicular hormones, testosterone and anti-mullerian hormone. In contrast, ovarian endocrine activity begins only after birth. The earliest phases of testicular hormone production are probably under autocrine or paracrine regulation, but the dependence on gonadotrophins starts in fetal life. During maturation of the hypothalamic-pituitary-testicular axis, the target organs acquire their responsiveness (viz receptors) before the onset of secretion of the tropic hormonal stimulus. The last link to develop is the feedback regulation, and the whole axis is functional in the developing male rat during the last days of gestation. Although gonadotrophin secretion starts in both sexes simultaneously, the fetal ovary is endocrinologically quiescent--its gonadotrophin responsiveness and endocrine activity begin only after birth. The fetal and postnatal periods of testicular activity have crucial effects on male sexual differentiation, whereas in the female, early sexual development occurs autonomously without influence of ovarian function. The purpose of this review is to elucidate some of the recent findings on the molecular mechanisms involved in the perinatal maturation of the rat hypothalamic-pituitary-gonadal axis.

scholarly journals Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 909
Author(s):  
Anyela Valentina Camargo Rodriguez
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Computational Modelling ◽  
Plant Morphology ◽  
Reproductive Organs ◽  
Biological Trait ◽  
Cereal Grain ◽  
Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

scholarly journals Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 782
Author(s):  
Veronica Tisato ◽  
Juliana A. Silva ◽  
Giovanna Longo ◽  
Ines Gallo ◽  
Ajay V. Singh ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Mthfr Gene ◽  
Spectrum Disorder ◽  
Fetal Life ◽  
Clinical Phenotypes ◽  
One Carbon Metabolism ◽  
Causes And Risk Factors ◽  
Individual Disease

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting behavior and communication, presenting with extremely different clinical phenotypes and features. ASD etiology is composite and multifaceted with several causes and risk factors responsible for different individual disease pathophysiological processes and clinical phenotypes. From a genetic and epigenetic side, several candidate genes have been reported as potentially linked to ASD, which can be detected in about 10–25% of patients. Folate gene polymorphisms have been previously associated with other psychiatric and neurodegenerative diseases, mainly focused on gene variants in the DHFR gene (5q14.1; rs70991108, 19bp ins/del), MTHFR gene (1p36.22; rs1801133, C677T and rs1801131, A1298C), and CBS gene (21q22.3; rs876657421, 844ins68). Of note, their roles have been scarcely investigated from a sex/gender viewpoint, though ASD is characterized by a strong sex gap in onset-risk and progression. The aim of the present review is to point out the molecular mechanisms related to intracellular folate recycling affecting in turn remethylation and transsulfuration pathways having potential effects on ASD. Brain epigenome during fetal life necessarily reflects the sex-dependent different imprint of the genome-environment interactions which effects are difficult to decrypt. We here will focus on the DHFR, MTHFR and CBS gene-triad by dissecting their roles in a sex-oriented view, primarily to bring new perspectives in ASD epigenetics.

scholarly journals Ovarian tissue freezing and activation after thawing: an update

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Li-fan Peng
Keyword(s):  
Granulosa Cells ◽  
Clinical Decision Making ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Clinical Decision ◽  
The Body ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Main Body ◽  
Tissue Cryopreservation

Abstract Background With the growth of women’s age, ovarian failure can be caused by various factors. For the women who need chemotherapy because of cancer factors, the preservation of fertility is more urgent. The treatment of cancer is also a process in which all tissues and organs of the body are severely damaged, especially in the reproductive system. Main body As a new fertility preservation technology, autologous ovarian tissue cryopreservation and transplantation is developing rapidly and showing great potentiality in preserving ovarian endocrine function of young cervical cancer patients. Vitrification and slow freezing are two common techniques applied for ovarian tissue cryopreservation. Thus, cryopreserved/thawed ovarian tissue and transplantation act as an important method to preserve ovarian function during radiotherapy and chemotherapy, and ovarian cryopreservation by vitrification is a very effective and extensively used method to cryopreserve ovaries. The morphology of oocytes and granulosa cells and the structure of organelles were observed under the microscope of histology; the hormone content in the stratified culture medium of granulosa cells with the diameter of follicle was used to evaluate the development potential of ovarian tissue, and finally the ovarian tissue stimulation was determined by the technique of ovarian tissue transplantation. Conclusions Although there are some limitations, the team members still carry out this review to provide some references and suggestions for clinical decision-making and further clinical research.

scholarly journals Protease Inhibitor Anti-HIV, Lopinavir, Impairs Placental Endocrine Function

2021 ◽  
Vol 22 (2) ◽  
pp. 683
Author(s):  
Camille Fraichard ◽  
Fidéline Bonnet-Serrano ◽  
Christelle Laguillier-Morizot ◽  
Marylise Hebert-Schuster ◽  
René Lai-Kuen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Metastatic Lymph Node ◽  
Endocrine Function ◽  
Maternal Circulation ◽  
Hormone Production ◽  
Mitofusin 2 ◽  
Villous Trophoblast ◽  
Activating Transcription Factor ◽  
Upr Pathway

Protease Inhibitors (PI e.g., ritonavir (RTV) and lopinavir (LPV)) used to treat pregnant mothers infected by HIV induce prematurity and endocrine dysfunctions. The maintenance of pregnancy relies on placental hormone production (human Chorionic Gonadotrophin (hCG) and progesterone (P4)). Those functions are ensured by the villous trophoblast and are mainly regulated by the Unfolded Protein Response (UPR) pathway and mitochondria. We investigated, in vitro, if PI impair hCG and P4 production and the potential intracellular mechanisms involved. Term villous cytotrophoblast (VCT) were cultured with or without RTV or LPV from 6 to 48 h. VCT differentiation into syncytiotrophoblast (ST) was followed measuring hCG and P4 secretion. We evaluated the expression of P4 synthesis partners (Metastatic Lymph Node 64 (MLN64), cholesterol side-chain cleavage (P450SCC), Hydroxy-delta-5-Steroid Dehydrogenase and 3 Beta-and steroid delta-isomerase 1 (HSD3B1)), of mitochondrial pro-fusion factors (Mitofusin 2 (Mfn2), Optic Atrophy 1 (OPA1)) and of UPR factors (Glucose-Regulated Protein 78 (GRP78), Activating Transcription Factor 4 (ATF4), Activating Transcription Factor 6 (ATF6), spliced X-box Binding Protein 1 (sXBP1)). RTV had no significant effect on hCG and P4 secretion, whereas lopinavir significantly decreased both secretions. LPV also decreased P450SCC and HSD3B1 expression, whereas it increased Mfn2, GRP78 and sXBP1 expression in ST. RTV has no effect on the endocrine placenta. LPV impairs both villous trophoblast differentiation and P4 production. It is likely to act via mitochondrial fusion and UPR pathway activation. These trophoblastic alterations may end in decreased P4 levels in maternal circulation, inducing prematurity.

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

2017 ◽  
Vol 176 (6) ◽  
pp. R283-R308 ◽  
Author(s):  
Evanthia Diamanti-Kandarakis ◽  
Maurizio Dattilo ◽  
Djuro Macut ◽  
Leonidas Duntas ◽  
Efstathios S Gonos ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Molecular Mechanisms ◽  
Dynamic Effect ◽  
The Elderly ◽  
Time Dependent ◽  
Endocrine Function ◽  
Scientific Society ◽  
Physiological Functions ◽  
Environmental Stimuli

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic–pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

Inhibitory Effect of Tributyltin on Expression of Steroidogenic Enzymes in Mouse Testis

2008 ◽  
Vol 27 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Suel-Kee Kim ◽  
Jong-Hoon Kim ◽  
Jung Ho Han ◽  
Yong-Dal Yoon
Keyword(s):  
Germ Cells ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Hydroxysteroid Dehydrogenase ◽  
Reproductive Organs ◽  
Inhibitory Effect ◽  
Testicular Development ◽  
Steroidogenic Enzymes ◽  
Hormone Production ◽  
Induced Apoptosis

Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17–20 lyase (P45017α), 3β-hydroxysteroid-dehydrogenase (3β-HSD), and 17β-hydroxysteroid-dehydrogenase (17β-HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.

Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy

1991 ◽  
Vol 125 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Takeshi Maruo ◽  
Hiroya Matsuo ◽  
Matsuto Mochizuki
Keyword(s):  
Thyroid Hormone ◽  
Early Pregnancy ◽  
Direct Consequence ◽  
Endocrine Function ◽  
Aromatase Activity ◽  
Maximum Increase ◽  
Stimulatory Action ◽  
Endocrine Activity ◽  
Estradiol 17Β

Abstract. Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10−8 mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17β as well as hCGα, hCGβ, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17β secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10−8 mol/l) enhances 3β-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10−8 mol/l) on the trophoblast endocrine function were also found with the use of T4 (10−7 mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.

scholarly journals Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects

2021 ◽  
Vol 22 (22) ◽  
pp. 12329
Author(s):  
Alfredo Ulloa-Aguirre ◽  
Teresa Zariñán ◽  
Eduardo Jardón-Valadez
Keyword(s):  
Plasma Membrane ◽  
G Protein ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Therapeutic Interventions ◽  
Endocrine Function ◽  
Receptor Protein ◽  
G Protein Coupled

Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes insipidus, thyroid disorders, familial hypocalciuric hypercalcemia, obesity, familial glucocorticoid deficiency [melanocortin-2 receptor, MC2R (also known as adrenocorticotropin receptor, ACTHR), and reproductive disorders. In these mutant receptors, misfolding leads to endoplasmic reticulum retention, increased intracellular degradation, and deficient trafficking of the abnormal receptor to the cell surface plasma membrane, causing inability of the receptor to interact with agonists and trigger intracellular signaling. In this review, we discuss the mechanisms whereby mutations in GPCRs involved in endocrine function in humans lead to misfolding, decreased plasma membrane expression of the receptor protein, and loss-of-function diseases, and also describe several experimental approaches employed to rescue trafficking and function of the misfolded receptors. Special attention is given to misfolded GPCRs that regulate reproductive function, given the key role played by these particular membrane receptors in sexual development and fertility, and recent reports on promising therapeutic interventions targeting trafficking of these defective proteins to rescue completely or partially their normal function.

scholarly journals Steroidal Androgens and Nonsteroidal, Tissue-Selective Androgen Receptor Modulator, S-22, Regulate Androgen Receptor Function through Distinct Genomic and Nongenomic Signaling Pathways

2008 ◽  
Vol 22 (11) ◽  
pp. 2448-2465 ◽  
Author(s):  
Ramesh Narayanan ◽  
Christopher C. Coss ◽  
Muralimohan Yepuru ◽  
Jeffrey D. Kearbey ◽  
Duane D. Miller ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Levator Ani ◽  
Reproductive Organs ◽  
Cross Reactivity ◽  
Levator Ani Muscle ◽  
Xenopus Laevis Oocyte ◽  
Muscle Weight

Abstract Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.

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