33 research outputs found
Inhibition of the glucocorticoidâactivating enzyme 11ÎČâhydroxysteroid dehydrogenase type 1 drives concurrent 11âoxygenated androgen excess
Aldoâketo reductase 1C3 (AKR1C3) is a key enzyme in the activation of both classic and 11âoxygenated androgens. In adipose tissue, AKR1C3 is coâexpressed with 11ÎČâhydroxysteroid dehydrogenase type 1 (HSD11B1), which catalyzes not only the local activation of glucocorticoids but also the inactivation of 11âoxygenated androgens, and thus has the potential to counteract AKR1C3. Using a combination of in vitro assays and in silico modeling we show that HSD11B1 attenuates the biosynthesis of the potent 11âoxygenated androgen, 11âketotestosterone (11KT), by AKR1C3. Employing ex vivo incubations of human female adipose tissue samples we show that inhibition of HSD11B1 results in the increased peripheral biosynthesis of 11KT. Moreover, circulating 11KT increased 2â3 fold in individuals with type 2 diabetes after receiving the selective oral HSD11B1 inhibitor AZD4017 for 35 days, thus confirming that HSD11B1 inhibition results in systemic increases in 11KT concentrations. Our findings show that HSD11B1 protects against excess 11KT production by adipose tissue, a finding of particular significance when considering the evidence for adverse metabolic effects of androgens in women. Therefore, when targeting glucocorticoid activation by HSD11B1 inhibitor treatment in women, the consequently increased generation of 11KT may offset beneficial effects of decreased glucocorticoid activation
Association of Spermatogenic Failure with the b2/b3 Partial AZFc Deletion
Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3)
Mutations in the protamine locus: association with spermatogenic failure?
abstract: The protamine locus consists of a 28.5 kb region with a linear array of the protamine (PRM)1, PRM2, PRM3 and transition nuclear protein (TNP)2 genes. Several studies indicate an abnormal expression pattern of protamine genes associated with male infertility, although the molecular mechanism underlying this observation is unclear. Here, we determined the spectrum of DNA variants present in all four genes in men with unexplained infertility compared with an ancestry-matched fertile/normospermic population. A total of 160 control individuals and at least 125 infertile men with either idiopathic azoospermia or oligozoospermia were sequenced for the open reading frame of PRM1, PRM2, PRM3 and TNP2 genes. All individuals carried an apparently intact Y chromosome. Of the 28 variants identified, 21 were previously described in the literature. The novel variants that were observed only in the infertile cohort included the SNP c.65G.A mutation which resulted in an amino acid change at the codon 22 (p.Ser22Asn) in the PRM1 gene, a mutation in the promoter region of PRM2 (267C.T) and a nonsense mutation in the PRM3 gene. These data are consistent with that of previous studies which have indicated that mutations in the protamine locus may be an infrequent cause of male infertility
Blends of hyaluronic acid derivatives with ethylene-vinyl alcohol copolymers as potential biomaterials
Single Nucleotide Polymorphism in Protamine 1 and Protamine 2 genes in fertile and infertile for men of Al-Najaf City
Online methods in geography educational research
Online methods in geography educational researc
Parenting gone wired: empowerment of new mothers on the Internet?
The extension of information and communication technologies is purported to provide great opportunities for women, with the potential for empowerment and feminist activism. This paper contributes to the debate about women and cyberspace through a focus on the role of the internet in the lives of a group of technologically proficient, socially advantaged white heterosexual new mothers. The internet played a central role in providing virtual social support and alternative information sources which increased these womenâs real sense of empowerment in the transition to motherhood. Simultaneously, however, very traditional stereotypes of mothering and gender roles persisted. A paradox is evident whereby the internet was both liberating and constraining: it played an important social role for some women while at the same time it encouraged restrictive and unequal gender stereotypes in this particular community of practice. An examination of new virtual parenting spaces therefore has a contribution to make in understanding changing parenting practices in the new millennium.
L'expansion des technologies de l'information et de la communication est censĂ©e pouvoir offrir de multiples possibilitĂ©s aux femmes susceptibles de renforcer leur autonomie et le militantisme fĂ©ministe. Cet article apporte un Ă©clairage au dĂ©bat sur les femmes et le cyberespace en examinant le rĂŽle de l'Internet dans les vies d'un groupe composĂ© de nouvelles mĂšres de race blanche, hĂ©tĂ©rosexuelle, socialement plus avantagĂ©es et maĂźtrisant les nouvelles technologies. L'Internet a jouĂ© un rĂŽle primordial dans le dĂ©veloppement d'un milieu de soutien social virtuel et l'offre de sources alternatives d'informations qui ont permis d'accroĂźtre leur sentiment rĂ©el d'ĂȘtre autonome lors du passage au stade de la maternitĂ©. En parallĂšle, toutefois, les idĂ©es stĂ©rĂ©otypĂ©es traditionnelles du maternage et des rĂŽles sexospĂ©cifiques persistent. Un paradoxe Ă©merge entre l'effet libĂ©rateur et contraignant de l'Internet: celui-ci a jouĂ© un rĂŽle social important pour quelques femmes tandis qu'il a simultanĂ©ment favorisĂ© des stĂ©rĂ©otypes liĂ©s au genre restreignants et inĂ©gaux au sein de cette communautĂ© de pratique. L'Ă©tude des nouveaux espaces virtuels qui encadrent le mĂ©tier de parent sert donc Ă mieux comprendre les pratiques des parents au nouveau millĂ©naire.
Se sugiere que el aumento de tecnologĂas de informĂĄtica y comunicaciĂłn les ofrece grandes oportunidades a las mujeres, con la posibilidad de empoderamiento y activismo feminista. Este papel contribuye al debate sobre mujeres y el ciberespacio por medio de un estudio del papel del internet en las vidas de un grupo de madres nuevas, blancas y heterosexuales, privilegiadas socialmente y muy competentes en el uso de nuevas tecnologĂas. El internet jugaba un papel importante al ofrecerles apoyo social virtual y fuentes alternativos de informaciĂłn, lo cual aumentaba el sentido de poder real que tenĂan estas mujeres en la transiciĂłn hacia la maternidad. Sin embargo, simultaneamente, persistĂan estereotipos muy tradicionales de la maternidad y los papeles de los gĂ©neros. ExistĂa una paradoja en que el internet les liberaba tanto como les limitaba. Jugaba un papel social importante para algunas mujeres pero, al mismo tiempo, fomentaba estereotipos de gĂ©nero limitantes y desiguales en esta comunidad de prĂĄctica. Como consecuencia, este estudio de nuevos espacios virtuales para madres tiene algo que contribuir a nuestro entendimiento de cambios en las prĂĄcticas de criar a los hijos en el nuevo milenio