025. Prolactin signaling through the short form of its cognate receptor causes severe ovarian defect

2005 ◽  
Vol 17 (9) ◽  
pp. 68
Author(s):  
G. Gibori ◽  
J. Halpern ◽  
C. Stocco ◽  
P. Kelly ◽  
N. Binart
Keyword(s):  
Premature Ovarian Failure ◽  
Short Form ◽  
Ovarian Failure ◽  
Specific Gene ◽  
Steroidogenic Enzyme ◽  
Prolactin Signaling ◽  
Long Form ◽  
Membrane Bound ◽  
First Time

Extensive investigations from our laboratory have clarified the action and interaction of estradiol (E) and prolactin (PRL) on corpus luteum (CL) function. Our research has led us to discover and isolate a CL specific gene that encodes a protein we named PRAP, that associates with the intracellular domain of the short form (PRLRS) but not the long form (PRLRL) and whose expression is tightly regulated by E. Our laboratory and others have established that this protein, expressed in CL of every species investigated, is a novel 17 beta hydroxysteroid dehydrogenase (17bHSD-7) whose function is to catalyze the transformation of estrone to E. Our results with cells expressing only PRLRS revealed that PRL acting through PRLRS leads to phosphorylation of PRAP/17bHSD-7 (PRAP/17b) by JAK2 establishing for the first time that a steroidogenic enzyme can be phosphorylated through its association with a membrane bound protein. The association of PRAP/17b with the PRLRS and its phosphorylation leads to its stabilization. To further investigate the role of PRL signaling through PRLRS, we used PRLR(–/–) mice expressing the PRLRS as a transgene. The results obtained were totally unexpected and of great interest. The follicles of the ovaries, expressing PRLRS only, underwent premature development followed by severe granulosa and oocyte death leaving holes surrounding collapsed zona pellucida and premature ovarian failure. The observations that: (1) the expression of PRLRS in the ovaries of PRL null mice leads to inhibition in Foxo3a and of GALT, two proteins whose deletion/mutation causes similar premature ovarian failure; and (2) that GALT promoter activity is stimulated by Foxo3a transcription factor led us to hypothesize that PRL acting through PRLRS prevents the expression of Foxo3a, which normally stimulates GALT transcriptional activity. Absence of Foxo3a then leads to inhibition of GALT and increases in galactose and its metabolites, causing galactose toxicity and granulosa as well as oocyte cell death.

scholarly journals Prolactin Signaling through the Short Form of Its Receptor Represses Forkhead Transcription Factor FOXO3 and Its Target Gene Galt Causing a Severe Ovarian Defect

2008 ◽  
Vol 22 (2) ◽  
pp. 513-522 ◽  
Author(s):  
Julia Halperin ◽  
Sangeeta Y. Devi ◽  
Shai Elizur ◽  
Carlos Stocco ◽  
Aurora Shehu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Premature Ovarian Failure ◽  
Target Gene ◽  
Short Form ◽  
Biological Activities ◽  
Follicular Development ◽  
Ovarian Failure ◽  
Forkhead Transcription Factor ◽  
Prolactin Signaling ◽  
Ovarian Pathology

Abstract Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation.

Role of the Different Sexuality Domains on the Sexual Function of Women with Premature Ovarian Failure

2015 ◽  
Vol 12 (3) ◽  
pp. 685-689 ◽  
Author(s):  
Cristina Laguna Benetti‐Pinto ◽  
Patrícia Magda Soares ◽  
Helena Patrícia Donovan Giraldo ◽  
Daniela Angerame Yela
Keyword(s):  
Sexual Function ◽  
Premature Ovarian Failure ◽  
Ovarian Failure

scholarly journals Cytogenetics of Premature Ovarian Failure: An Investigation on 269 Affected Women

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Simona Baronchelli ◽  
Donatella Conconi ◽  
Elena Panzeri ◽  
Angela Bentivegna ◽  
Serena Redaelli ◽  
...  
Keyword(s):  
X Chromosome ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Population Group ◽  
Ovarian Failure ◽  
Chromosome Mosaicism ◽  
Low Level

The importance of X chromosome in the aetiology of premature ovarian failure (POF) is well-known but in many cases POF still remains idiopathic. Chromosome aneuploidy increase is a physiological phenomenon related to aging, but the role of low-level sex chromosome mosaicism in ovarian function is still undiscovered. Standard cytogenetic analysis was carried out in a total of 269 patients affected by POF: 27 chromosomal abnormalities were identified, including X chromosome and autosomal structural and numerical abnormalities. In 47 patients with 46,XX karyotype we performed interphase FISH using X alpha-satellite probe in order to identify X chromosome mosaicism rate. Aneuploidy rate in the patient group was significantly higher than the general population group. These findings underline the importance of X chromosome in the aetiology of POF and highlight the potential role of low-level sex chromosome mosaicism in ovarian aging that may lead to a premature onset of menopause.

scholarly journals SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70

2008 ◽  
Vol 28 (20) ◽  
pp. 6384-6401 ◽  
Author(s):  
Nagalingam R. Sundaresan ◽  
Sadhana A. Samant ◽  
Vinodkumar B. Pillai ◽  
Senthilkumar B. Rajamohan ◽  
Mahesh P. Gupta
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Gene Regulation ◽  
Essential Role ◽  
Short Form ◽  
Biological Functions ◽  
Proapoptotic Protein ◽  
Long Form ◽  
And Oxidative Stress

ABSTRACT There are seven SIRT isoforms in mammals, with diverse biological functions including gene regulation, metabolism, and apoptosis. Among them, SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans. In this study, we examined the role of SIRT3 in murine cardiomyocytes. We found that SIRT3 is a stress-responsive deacetylase and that its increased expression protects myocytes from genotoxic and oxidative stress-mediated cell death. We show that, like human SIRT3, mouse SIRT3 is expressed in two forms, a ∼44-kDa long form and a ∼28-kDa short form. Whereas the long form is localized in the mitochondria, nucleus, and cytoplasm, the short form is localized exclusively in the mitochondria of cardiomyocytes. During stress, SIRT3 levels are increased not only in mitochondria but also in the nuclei of cardiomyocytes. We also identified Ku70 as a new target of SIRT3. SIRT3 physically binds to Ku70 and deacetylates it, and this promotes interaction of Ku70 with the proapoptotic protein Bax. Thus, under stress conditions, increased expression of SIRT3 protects cardiomyocytes, in part by hindering the translocation of Bax to mitochondria. These studies underscore an essential role of SIRT3 in the survival of cardiomyocytes in stress situations.

A dimeric catalytic core relates the short and long forms of ATP-phosphoribosyltransferase

2018 ◽  
Vol 475 (1) ◽  
pp. 247-260 ◽  
Author(s):  
Gerd Mittelstädt ◽  
Wanting Jiao ◽  
Emma K. Livingstone ◽  
Gert-Jan Moggré ◽  
Ali Reza Nazmi ◽  
...  
Keyword(s):  
Short Form ◽  
Allosteric Regulation ◽  
Regulatory Domain ◽  
Molecular Architecture ◽  
Histidine Biosynthesis ◽  
Catalytic Core ◽  
Catalytic Domains ◽  
Long Form ◽  
Covalently Linked ◽  
First Time

Adenosine triphosphate (ATP) phosphoribosyltransferase (ATP-PRT) catalyses the first committed step of histidine biosynthesis in plants and microorganisms. Two forms of ATP-PRT have been reported, which differ in their molecular architecture and mechanism of allosteric regulation. The short-form ATP-PRT is a hetero-octamer, with four HisG chains that comprise only the catalytic domains and four separate chains of HisZ required for allosteric regulation by histidine. The long-form ATP-PRT is homo-hexameric, with each chain comprising two catalytic domains and a covalently linked regulatory domain that binds histidine as an allosteric inhibitor. Here, we describe a truncated long-form ATP-PRT from Campylobacter jejuni devoid of its regulatory domain (CjeATP-PRTcore). Results showed that CjeATP-PRTcore is dimeric, exhibits attenuated catalytic activity, and is insensitive to histidine, indicating that the covalently linked regulatory domain plays a role in both catalysis and regulation. Crystal structures were obtained for CjeATP-PRTcore in complex with both substrates, and for the first time, the complete product of the reaction. These structures reveal the key features of the active site and provide insights into how substrates move into position during catalysis.

Saving the silent voyager: Mapping virtues in the writing of Eva Sommer, Australia’s first Walkley Award winner

2020 ◽  
Vol 42 (2) ◽  
pp. 261-277
Author(s):  
Jennifer Martin
Keyword(s):  
Analytical Tool ◽  
Holocaust Survivor ◽  
Journalism History ◽  
Award Winner ◽  
Rightful Place ◽  
Long Form ◽  
First Time ◽  
Form Feature

In 1956, 22-year-old cadet journalist Eva Sommer won Australia’s first Walkley Award for a story about a supposedly stateless stowaway who was ‘doomed’ to sail between Italy and Australia because he had lost his memory. Sommer’s dedicated reporting skills revealed the man was a traumatized Holocaust survivor from Poland who had been granted asylum in Australia five years earlier. A ‘girl reporter’ had achieved in two days what immigration officials from two countries had failed to achieve in three months. Yet, despite Sommer’s remarkable story and her status as the inaugural Walkley winner, little is known of her writing or her life. This article aims to reinstate Eva Sommer to her rightful place in Australia’s journalism history through an analysis of how her three articles on the stowaway communicated emotions and virtues to readers. For the first time I will apply the Virtue Map, my analytical tool for examining the role of emotion and virtues in journalism, to a series of articles instead of a single long-form feature, illuminating a forgotten moment of Australia’s journalism history.

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