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      Androgen Receptors Expression in Pituitary of Male Viscacha in relation to Growth and Reproductive Cycle

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          Abstract

          The aim of this work was to study the androgen receptors (AR) expression in pituitary pars distalis (PD) of male viscachas in relation to growth and reproductive cycle. AR were detected by immunocytochemistry and quantified by image analysis. Pituitary glands from fetus, immature, prepubertal, and adult viscachas during their reproductive cycle were used. In the fetal PD, the immunoreactivity (ir) was mainly cytoplasmic. In immature and prepubertal animals, AR-ir was cytoplasmic (ARc-ir) and nuclear (ARn-ir) in medial region. In adult animals, ARn-ir cells were numerous at caudal end. AR regionalization varied between the PD zones in relation to growth. In immature animals, the ARn-ir increased whereas the cytoplasmic expression decreased in relation to the fetal glands. The percentage of ARc-ir cells increased in prepubertal animals whereas the nuclear AR expression was predominant in adult viscachas. The AR expression changed in adults, showing minimum percentage in the gonadal regression period. The variation of nuclear AR expression was directly related with testosterone concentration. These results demonstrated variations in the immunostaining pattern, regionalization, and number of AR-ir cells throughout development, growth, and reproductive cycle, suggesting the involvement of AR in the regulation of the pituitary activity of male viscacha.

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          Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B.

          Kisspeptin is a potent stimulator of GnRH secretion that has been implicated in the feedback actions of ovarian steroids. In ewes, the majority of hypothalamic kisspeptin neurons are found in the arcuate nucleus (ARC), with a smaller population located in the preoptic area. Most arcuate kisspeptin neurons express estrogen receptor-alpha, as do a set of arcuate neurons that contain both dynorphin and neurokinin B (NKB), suggesting that all three neuropeptides are colocalized in the same cells. In this study we tested this hypothesis using dual immunocytochemistry and also determined if kisspeptin neurons contain MSH or agouti-related peptide. To assess colocalization of kisspeptin and dynorphin, we used paraformaldehyde-fixed tissue from estrogen-treated ovariectomized ewes in the breeding season (n = 5). Almost all ARC, but no preoptic area, kisspeptin neurons contained dynorphin. Similarly, almost all ARC dynorphin neurons contained kisspeptin. In experiment 2 we examined colocalization of kisspeptin and NKB in picric-acid fixed tissue collected from ovary intact ewes (n = 9). Over three quarters of ARC kisspeptin neurons also expressed NKB, and a similar percentage of NKB neurons contained kisspeptin. In contrast, no kisspeptin neurons stained for MSH or agouti-related peptide. These data demonstrate that, in the ewe, a high percentage of ARC kisspeptin neurons also produce dynorphin and NKB, and we propose that a single subpopulation of ARC neurons contains all three neuropeptides. Because virtually all of these neurons express estrogen and progesterone re-ceptors, they are likely to relay the feedback effects of these steroids to GnRH neurons to regulate reproductive function.
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            Androgen action in the masculinization programming window and development of male reproductive organs.

            We have shown previously that deficient androgen action within a masculinization programming window (MPW; e15.5-e18.5 in rats) is important in the origin of male reproductive disorders and in programming male reproductive organ size, but that androgen action postnatally may be important to achieve this size. To further investigate importance of the MPW, we used two rat models, in which foetal androgen production or action was impaired during the MPW by exposing in utero to either di(n-butyl) phthalate (DBP) or to flutamide. Reduced anogenital distance (AGD) was used as a monitor of androgen production/action during the MPW. Offspring were evaluated in early puberty (Pnd25) to establish if reproductive organ size was altered. The testes, penis, ventral prostate (VP) and seminal vesicles (SV) were weighed and penis length measured. Both DBP and flutamide exposure in the MPW significantly reduced penis, VP and SV size along with AGD at Pnd25; AGD and organ size were highly correlated. In DBP-, but not flutamide-, exposed animals, testis weight was also reduced and correlated with AGD. Intratesticular testosterone was also measured in control and DBP-exposed males during (e17.5) or after (e21.5) the MPW and related to AGD at e21.5. To evaluate the importance of postnatal androgen action in reproductive organ growth, the effect of combinations of prenatal and postnatal maternal treatments on AGD and penis size at Pnd25 was evaluated. In prenatally DBP-exposed animals, further postnatal exposure to either DBP or flutamide significantly reduced AGD and penis size in comparison with prenatal DBP exposure alone. In comparison, rats exposed postnatally to testosterone propionate after prenatal vehicle-exposure showed considerable increase in these parameters vs. controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally.
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              The rules of DNA recognition by the androgen receptor.

              The androgen receptor (AR) and glucocorticoid, progestagen, and mineralocorticoid receptors all recognize classical DNA response elements that are organized as inverted repeats of 5'-AGAACA-3'-like motifs with a three-nucleotide spacer. Next to such elements, the AR also recognizes a second type of androgen response element (ARE), the so-called selective AREs, which resemble more the direct repeats of the same hexamer. In this work, we show that not only the AR but also the progestagen receptor can recognize the selective AREs, whereas neither glucocorticoid nor mineralocorticoid receptor can. Recently, genomic AR-binding fragments have been postulated to contain AR-binding sites that diverge considerably from the classical ARE consensus. Extensive mutational analyses of these candidate motifs, however, reinstalls the values of the consensus sequence for the AREs as mentioned above, the importance of their dimeric nature and the presence of exactly three-nucleotide spacing. We developed a position-specific probability matrix that was used to predict with higher accuracy new AREs in different AR-binding regions. So far, all AR-binding genomic fragments that were analyzed contain AREs defined as receptor-dimer binding motifs with the ability to confer responsiveness to a reporter gene.
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                Author and article information

                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi Publishing Corporation
                1687-8337
                1687-8345
                2015
                7 April 2015
                : 2015
                : 168047
                Affiliations
                1Histología, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Avenida Ejército de los Andes 950, Bloque I, Piso No. 1, 5700 San Luis, Argentina
                2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 5700 San Luis, Argentina
                Author notes
                *Fabian Heber Mohamed: fhmo@ 123456unsl.edu.ar

                Academic Editor: Małgorzata Kotula-Balak

                Article
                10.1155/2015/168047
                4405020
                7ede41ab-4087-421d-b8a7-1348d0481ed8
                Copyright © 2015 Verónica Palmira Filippa et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 November 2014
                : 6 March 2015
                : 8 March 2015
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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