Distribution Of Androgen Receptor Research Articles

Testosterone is closely related to Leydig cell activity, environmental factors, and androgen receptor distribution in adult male lizards of Liolaemus cuyanus (Reptilia: Liolaemidae) during the reproductive cycle.

Testosterone, the primary sex hormone in male lizards, is closely linked to Leydig cell activity (the cells where steroidogenesis occurs) throughout the reproductive cycle, but testosterone action is related to androgen receptors (ARs) distribution in the seminiferous epithelium. In temperate zones, environmental factors detected through the hypothalamic-pituitary-gonadal axis, downregulate plasma testosterone, resulting in a seasonal reproductive cycle. The aim of this work is to study plasma testosterone in adult male lizards of Liolaemus cuyanus, an oviparous species, throughout its reproductive cycle and its relationship with Leydig cell histology, TotalLeydigCell/ActiveLeydigCell (TLC/ALC) ratio, environmental factors (temperature, relative humidity and solar irradiation) and ARs distribution in seminiferous epithelium. Specimens (N = 27) were captured (October to March) in a semi-arid zone (Valle de Matagusanos, San Juan, Argentina) and grouped into three relevant reproductive periods: pre-reproductive (PrR), reproductive (R), and post-reproductive (PsR). Significant differences in plasma testosterone were found among these periods, highest during R than in PsR. A significant positive correlation between plasma testosterone and TLC/ALC ratio was also observed. Plasma testosterone has a significant positive correlation only with solar irradiation, but not with the other variables. In PrR and R, ARs distribution was cytoplasmic and nuclear, shifting to only cytoplasmic in PsR. These results highlight the close correspondence between plasma testosterone, Leydig cell histology and activity, environmental factors, and ARs distribution, resulting in a synchronization that allows males of L. cuyanus to coordinate their reproductive cycle with the most favorable environmental conditions, probably for mating and birth of offspring.

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model

Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor β (ERβ), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERβ and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERβ mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.

Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.

While immunotherapy has shown potent efficacy in clinical practices, patient selection to receive checkpoint blockade is still challenging in prostate cancer (PCa). LAT and ZAP70 functions in lymphocyte activation and plays a critical role in T cell receptor (TCR) signal transduction. However, PCa genomic and clinical data regarding the role of LAT and ZAP70 are limited. We aim to identify and characterize LAT/ZAP70 defined subtypes of PCa. We elaborated the TCGA PCa data and metastatic castration-resistant prostate cancer (mCRPC) RNA-seq data bioinformatic analysis and systematically elucidated the role of intra-tumoral expressed LAT and ZAP70 in the progression-free survival and immunotherapeutic-related signals. LAT/ZAP70-associated immune infiltration was evaluated using bioinformatic tools. Immunohistochemical staining of serial sections was used to confirm the expression and distribution of LAT, ZAP70 and androgen receptor (AR) in PCa tissues. Specifically, LAT and ZAP70 revealed increased expressions in PCa when compared to normal tissues and positively associated with intra-tumoral immune cells infiltration. LAT/ZAP70 defined immune-high early-stage PCa revealed higher TP53 mutation frequency and poor prognosis. Transcriptome analysis indicated immune-related signals and CTLA4 expression were highly enhanced in immune-high PCa parallel with higher protein level of MYC and lower AR expression. In mCRPC, LAT/ZAP70 defined immune-high patients also revealed upregulated immune related signals, higher CTLA4 expression and DNA repair deficiency. LAT/ZAP70 defined immune-high PCa linked to immune infiltration and predicts poor prognosis. Immune-high PCa may receive effective response from immune checkpoint inhibitor parallel with systemic treatment.

Effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep.

The effects of androgens on human skin mainly include the regulation of growth and differentiation of hair follicles and sebaceous glands. Androgens may have some physiological roles in sheep skin that are similar to those of humans, but further confirmation is needed. Therefore, Hetian sheep were chosen in this study as an animal model to explore the effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep. The sheep were treated with different concentrations of testosterone for 42days. Skin tissue sections were prepared and then subjected to hematoxylin-eosin, Sacpic, Masson's trichrome, and Oil Red O staining to observe changes in skin morphology. Changes in the content of blood-related factors were also detected using ELISA kits. The skin tissue distribution of androgen receptor was explored by immunohistochemistry and immunofluorescence assays. The results showed that testosterone significantly increases the sebaceous gland area and stimulates the formation of new sebaceous glands. Further exploration revealed that testosterone promotes the proliferation of sebaceous gland juvenile cells. However, testosterone was found to have no significant effect on hair follicle density and hair follicle structure. Testosterone increased dihydrotestosterone levels but decreased 5α-reductase 1 and 5α-reductase 2 levels. The androgen receptors were distributed in the hair follicles, sebaceous glands, and some major skin appendages of Hetian sheep. This study suggests that androgens can be effective in regulating sebum production in sheep. This study will help advance research efforts to further explore the molecular and cellular mechanisms by which androgens modify sheep follicles and sebaceous glands.

Differences in SUV39H1 and androgen receptor distribution in adenomyomatous hyperplasia and prostatic adenocarcinoma

Androgen receptor (AR) contributes to the growth of both early- and late-stage prostate cancer. Overexpression of suppressor of variegation 3-9 homolog 1 (SUV39H1) increases migration of prostate cancer cells, while depletion of SUV39H1 suppresses migration of prostate cancer cells. In this study, the aim was to show the relationships of AR and SUV39H1 with adenomyomatous hyperplasia (AH) and prostate adenocarcinoma (PCa). 70 AH and 70 PCa preparations in Pathology Department from 2013 to 16 were retrospectively investigated. Samples with immunohistochemical staining for AR and SUV39H1 were evaluated with a light microscope. After pathologic investigation of samples, AR and SUV39H1 expressions were scored. The changes in the frequencies of the obtained scores in the AH and PCa groups were analyzed statistically. AR expression was observed to be greater in AH compared to PCa. This difference was found to be statistically significant (p = 0.003). SUV39H1 expression was identified to be greater in PCa compared to AH and this showed statistical significance (p = 0.031). PCa samples were identified to have nearly 1.5 times more SUV39H1 mild staining compared to AH samples and this increase was two times for SUV39H1 strong staining. In our study, AR expression was greater in AH compared to PCa samples. This situation is inverse to the known mechanism and cannot be clearly explained. It needs to be supported with large series and other prognostic parameters. This study observed increased SUV39H1 values in PCa compared to AH and from this aspect, it may be considered an important poor prognosis parameter.

Androgen and oestrogen receptors in the growing antlers velvet of adult and yearling pampas deer (Ozotoceros bezoarticus) males.

To determine the presence, quantity and distribution of androgen (AR) and oestrogen receptors (ER) in the antler velvet (AV), samples were collected from adult and yearling pampas deer males, as well as skin from the ventrolateral abdominal area (ASK). Samples were analysed with ligand-binding assays for AR and ER activity and processed for AR and ERβ immunohistochemistry. There was more content of AR in adults than in yearling males (p=0.02), as well as a category and type of tissue interaction (p=0.03). There was more ER content in adults than in yearling males (p=0.005) and in the AV than in the skin (p=0.0001). The AR-positive score (PS) was greater in AV than in ASK in the surface stroma (p=0.0007). In the intermediate epidermis, the AR PS was greater in adults than in yearling males (p=0.04) and in the ASK than in the AV (p<0.0001). There was a male category and type of tissue interaction for AR PS in the sebaceous glands (p=0.014). The ERβ PS in the surface stroma was greater in ASK than in AV (p=0.004) and tended to be greater in yearling than in adult males (p=0.093). The ERβ PS in the intermediate epithelium and the sebaceous glands was greater in adults than in yearlings (p=0.004 and p=0.007, respectively). In conclusion, we reported for the first time the presence of AR and ER in the velvet skin of growing antlers in pampas deer males. Therefore, the velvet skin is sensitive to both androgens and oestrogens. Furthermore, the greater content of oestrogen receptors in the velvet of adult males suggests that adults are more sensitive to this hormone than yearlings, and thus, oestrogens have greater importance in velvet activity regulation in adult males.

Paternal and infanticidal behavior in the Mongolian gerbil (Meriones unguiculatus): An approach to neuroendocrine regulation

This study aimed to provide evidence on estrogen and androgen pathways regulating the Mongolian gerbil's paternal and infanticidal behaviors (Meriones unguiculatus). We analyzed estrogen receptor alpha (ERα) and androgen receptor (AR) distribution in the medial preoptic area (mPOA), the bed nucleus of stria terminalis (BNST), as well as the anterior hypothalamic nucleus (AHN), the ventromedial hypothalamus nucleus (VMH), and the periaqueductal gray area (PAG) nuclei activated when males interact paternally or aggressively with the pups, respectively. Twenty aggressive males towards the pups and 10 paternal were selected through a screen paternal behavior test. Three groups of 10 males each were formed: paternal males (PAT), males with testosterone (T)-induced paternal behavior (T-PAT), and aggressive males (AGG). Male gerbils could interact with a pup for a few minutes, and their brains were removed and dissected for ERα and AR immunoreactivity (ir). The results showed that in T-PAT and PAT males, the number of ERα-ir and AR-ir cells in the mPOA/BNST was significantly higher than in AGG males. In AGG males, the number of ERα-ir and AR-ir cells in the AHN/VMH/PAG was significantly higher than PAT and T-PAT males. This difference in the presence of ERα and AR in nuclei activated in paternal interactions in the Mongolian gerbil supports the idea that these receptors participate in regulating paternal behavior. Also, these results suggest, for the first time, that they could be involved in the infanticidal behavior in this rodent.

Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia: A cross sectional study.

Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.

Effects of phthalates on bovine primary testicular culture and spermatozoa.

Among environmental endocrine-active chemicals, phthalates, commonly known as plasticizers, disrupt the development of the male reproductive tract. In this study, the effects of phthalates (DIBP, BBP, DINP, DBP, DEP, DEHP and DMP) were evaluated on cultures of bovine primary male reproductive cells (n = 3) and spermatozoa (n = 4). Epididymal (caput and corpus epididymis), testicular (parenchymal and mediastinal/tubular) and vas deferens cells (VDC) were prepared from samples collected from slaughterhouse. Second part of caput epididymis which have fewer amount of principal cells, were found to be less affected compared to the first part except DEHP; while corpus epididymis was found to be more affected with IC50 values below 0.976ng/mL (except for DEP at 4.97ng/mL). In testicular parenchymal cells, IC50 ranged from 0.15 to 4.11ng/mL and for mediastinum from 0.01 to 7.31ng/mL; where cytotoxic effects were more evident in mediastinal section. Least cytotoxic and even proliferational effects (DEHP, DMP and DEP) were observed in VDC, the muscular tube carrying sperm from epididymis to the ejaculatory duct. Least spermiotoxic phthalate was DBP (3.928ng/mL); while DINP (0.550ng/mL) induced highest cytotoxic effect on bovine spermatozoa. Differences in the cellular structure and/or the androgen receptor distribution effect the toxicity of phthalates. Our preliminary findings on bovine spermatozoa indicate possible morphological and motility alterations; which challenges further investigation of the transition of phthalates on semen straws used in cryopreservation. Increase of exposure to environmental contaminants raise the issue of the requirement of a new perspective on reproductive health, species and tissue specific differences should further be emphasized.

Prenatal and pubertal testosterone affect brain lateralization

After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency.

Androgen Receptor Expressed in Three Types of Testicular Cells and Played an Important Role in Reproductive System

Aims: To investigate the expression and distribution of Androgen Receptor in all kinds of testicular tissue cells, as well as its effect to reproductive system. Methods: Using immunofluorescence method to detect the mice testicular tissue after the paraffin section and then find out AR expression and distribution in testis cells. By constructing Ar knockout mice and observing its reproductive system phenotype to identify how AR affect the reproductive system. Results: AR have a strong signal in Sertoli cells, Peritubul myoid cells and Leydig cells but without any specific signal in Germ cells. Ar knockout mice changed penis position compared to control and the distance of its perineum became shorter, just seems like fake clitoris. The testicular volume of Ar knockout mice was significantly smaller and the cell species, distribution and proportion within the seminiferous tubules changed significantly. Conclusion: AR expressed in testis Sertoli cells, Peritubul myoid cells and Leydig cells except in germ cells. Ar knockout mice appeared feminization of male and its sperm was blocked during the early phase of the first meiosis.

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Seasonal morphophysiological variations in the prostatic complex of the Tarabul's gerbil (Gerbillus tarabuli).

Gerbillus tarabuli is a nocturnal Saharan rodent which has an annual reproductive cycle characterized by the reproductive activity in spring and a long phase of sexual quiescence in other seasons. We describe the morphology and hormonal regulation of the prostatic complex of this rodent in the two periods, based on anatomical, histological, morphometric, and immunohistochemical analyses. The organisation of this prostatic complex is similar to that reported for Meriones unguiculatus, but different from the prostate of Psammomys obesus, the rat, and the mouse. In addition to the anterior lobes, ventral lobes, and dorsal lobes, the prostatic complex of Gerbillus tarabuli, also includes dorsolateral lobe. Each lobe is composed of a fibro-muscular stroma surrounding a glandular epithelium. Dorsolateral lobes are easily distinguishable by their big volume. The prostate grows and regresses cyclically throughout the year. During the resting season, ventral lobes and anterior lobes showed atrophy, with a significant decrease in both epithelial height and supranuclear area size, and a strong thickening of the fibro-muscular compartment. In dorsal lobes, the epithelial and stromal compartments atrophied and regenerated simultaneously, whereas in dorsolateral lobe the thickness of the epithelium, the supranuclear zone and the stroma increased during resting period. Furthermore, seasonal variations were observed in the distribution and expression of both androgen receptors, and estrogens receptors. Expression patterns of all receptors were lobe-specific. In conclusion, both androgens and estrogens are involved in the homeostasis and regulation of the prostate in Gerbillus tarabuli. Dorsolateral lobe seems to be controlled by a different mechanism than other lobes.

Gender Difference in Distribution of Estrogen and Androgen Receptors in Intestinal-type Gastric Cancer

Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer. Immunohistochemical analysis was performed in 60 patients (42% females). In gastric cancer patients, frequency of ERα-positive cells was lower in epithelium than in healthy individuals, but not significantly. In stroma and epithelium, AR-positive cells were absent from samples of women with T1 and T2 stage disease, while in men, their frequency was significantly increased in stroma of those with T3 and T4 stages and was significantly higher compared to women. AR-positive cells in stroma were fibroblasts, myofibroblasts and mast cells. To our knowledge, this study is the first to show gender differences in the distribution and frequency of AR-positive cells in neoplastic stroma of gastric cancer.

Testosterone regulates birdsong in an anatomically specific manner

The functions of birdsong include attracting a mate and repelling competitors. It is therefore not surprising that, in males in the temperate zone especially, birdsong is often produced in the context of reproduction. Testosterone of gonadal origin increases during the reproductive phase of the annual cycle and can significantly influence song production as well as song development via effects on song crystallization (testosterone secretion at the time of sexual maturity is essential for full crystallization to occur). In males, testosterone of gonadal origin can exert its effects in the brain on song and other reproductive behaviour via its oestrogenic and androgenic metabolites. The widespread distribution of nuclear androgen receptors in the song system and the occurrence of oestrogen receptors in one key forebrain nucleus in certain species as well as the presence of both receptor types in the diencephalon and the midbrain raises questions as to where and how testosterone is exerting its myriad effects on song. By selectively implanting testosterone into specific brain regions of castrated male canaries, Serinus canaria, we have identified the medial preoptic area as a critical site for the induction of a generalized increase in motivation that includes the motivation to sing. Testosterone action in the forebrain song nucleus HVC in contrast increases song stereotypy. Canaries receiving testosterone in the preoptic area and HVC sing stereotypic songs but at a much lower amplitude, indicating that testosterone's effects on amplitude are regulated elsewhere in the brain or the periphery. The lateral part of the magnocellular nucleus anterior nidopallium (LMAN) is a song nucleus that expresses a high density of androgen receptors and plays a role as a song variability generator during song learning. When adult female canaries are treated with testosterone, their song becomes more complex. Lesions to LMAN attenuate these effects on adult behavioural change, suggesting that testosterone may act in LMAN during song ontogeny to modulate changes associated with song crystallization. These anatomically specific effects illustrate how a single hormone can coordinate changes in many aspects of a complex behaviour to facilitate successful reproduction.

Immunohistochemistry Study on Androgen and Estrogen Receptors of Rat Seminal Vesicle Submitted to Simultaneous Alcohol-Nicotine Treatment.

Alcohol consumption is habitually accompanied by the use of other psychoactive substances, mostly tobacco. Nicotine and alcohol affect male accessory reproductive glands function. Most studies have been done on pathologic features of prostate, but there has been no systematic study on the seminal vesicle. Therefore, the aim of current study was to investigate the distribution of androgen receptor (AR) and estrogen receptors-beta (ER-β) immune reactivities following long-term treatment of alcohol, nicotine or a combination of both substances. In this experimental study, a total of 40 adult Wistar rats, nine weeks of age, were used. Animals were randomly divided into four groups, including: i. Control group receiving normal saline 0.09%, ii. Ethanol group receiving ethanol 20% (2 ml/kg, via gavage), iii. Nicotine group receiving nicotine (0.1 mg/kg, subcutaneous injection), and iv. Ethanol-nicotine group receiving simultaneous ethanol 20% (2 ml/kg) and nicotine (0.1 mg/kg) treatment. All treatment lasted for eight weeks. Prior to intracardiac perfusion, blood sample was collected from left ventricle. The seminal vesicles were isolated and processed for paraffin blocking. The sample tissues were then studied for distribution of AR and ER-β immunereactivities using immunohistochemical (IHC) staining method. One way analysis of variance (ANOVA) and Tukey's test were performed for data analysis. A value of P<0.05 was considered significant. Our results revealed that the lowest mean number of positive cells belonged to the animals of ethanol-nicotine group that was followed by the ethanol, nicotine, and control groups, respectively. However, there was no significant difference regarding serum testosterone level among experimental groups. It was concluded that combination of both ethanol and nicotine may be a crucial factor in the expression levels of AR and ER-β.

Androgen receptor distribution in the rat prostate gland and seminal vesicles

To better understand the effect of androgen on the growth and function of accessory sex glands, it can be useful to determine the presence or absence of the androgen receptor (AR) in the individual cell types. Five adult intact male rats were sacrificed at 120 days. Their seminal vesicles and prostate glands were removed, fixed in Bouin's fixative and embedded in paraffin wax. The tissues were sectioned at 5 μm and stained using the microwave-stimulated antigen retrieval technique for immunohistochemistry. Positive immunohistochemical staining for the AR was evident in nuclei but not in the cytoplasm of gland cells such as luminal cells, basal cells, periacinar smooth muscle cells, other stromal cells, and smooth muscle cells in the tunica muscularis. The proportions of AR-positive and AR-negative basal cells were similar. The staining intensity of luminal cells was greater than basal cells and stromal cells. The numbers of AR-positive and AR-negative luminal cells in the prostate were almost equal. On the other hand, in the seminal vesicle only a small number of luminal cells were AR-negative. These observations can be interpreted to mean that the epithelium of the seminal vesicle is more sensitive to androgenic stimulation than the prostate epithelium.

Neurones in the preoptic area of the male goldfish are activated by a sex pheromone 17α,20β-dihydroxy-4-pregnen-3-one.

Pheromones are interesting molecules given their ability to evoke changes in the endocrine state and behaviours of animals. In goldfish, a sex pheromone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P), which is released by preovulatory females, is known to trigger the elevation of luteinising hormone (LH) levels, as well as reproductive behaviour in males. Interestingly, when 11-ketotestosterone (11-KT) is implanted into adult female fish, LH levels increase in response to the pheromone at any time of the day, which is normally a male-specific response. However, the neural mechanisms underlying the male-specific information processing of 17,20β-P and its androgen dependence are yet unknown. In the present study, we focused on the preoptic area (POA), which plays important roles in the regulation of reproduction and reproductive behaviours. We mapped activity in the POA evoked by 17,20β-P exposure using the immediate-early gene c-fos. We found that a population of ventral POA neurones close to kisspeptin2 (kiss2) neurones that appear to have important roles in reproduction was activated by 17,20β-P exposure, suggesting that these activated neurones are important for the 17,20β-P response. Next, we investigated the distribution of androgen receptor (ar) in the POA and its relationship with 17,20β-P-responsive and kiss2 neurones. We found that ar is widely expressed in the ventral POA, whereas it is only expressed in approximately 10% of 17,20β-P-activated neurones. On the other hand, it is expressed in almost 90% of the kiss2 neurones. Taken together, it is possible that ar expressing neurones in the ventral POA, most of which were not labelled by c-fos in the present study, may at least partly account for androgen effects on responses to primer pheromones; the ar-positive kiss2 neurones in the ventral POA may be a candidate. These results offer a novel insight into the mechanisms underlying male-specific information processing of 17,20β-P in goldfish.

Expression of estrogen and androgen receptors in tissues of external genitalia of girls with congenital adrenal hyperplasia

The reason of post-operative introital stenosis in girls with CAH is a poor estrogenization of external genitalia before vaginoplasty. It is possible that the local sensitivity to estrogens can be reduced due to prenatal androgen excess in addition to inadequate compensation, which results to decrease of estrogens production by the ovaries. Objective. To determine the distribution of estrogen and androgen receptors in genital tissue, depending on the form of CAH, the degree of external virilization and serum levels of androgens. Material and methods. The waste surgical tissues obtained during routine feminizing genitoplasty (clitoro- and vaginoplasty) was used for immunohistochemical study of estrogen (α and β) and androgen receptors in girls with CAH (n=13 and n=8, respectively). Results. The expression of estrogen (α, β) and androgen receptors was determined in genital tissues of girls with CAH. There was no significant correlation between the number of immunopositive cells in the tissues of labia minora and vagina and the degree of virilization, as well as between the number of cells expressing the receptors and serum levels of androgens (testosterone, 17-hydroxyprogesterone). There was no difference in the expression of estrogen and androgen receptors between girls with salt-wasting and simple virilizing forms of CAH. The expression of estrogen receptor α in vaginal tissues was reduced in girls who underwent repeated vaginoplasty and were under preoperative local estrogen therapy in comparison to patients in whom the vaginoplasty was performed for the first time (p=0.045). Conclusion. The distribution of estrogen and androgen receptors in the labial and vaginal tissues in girls with CAH doesn’t depend on the form of disease, external virilization and serum levels of androgens. Girls undergoing repeated vaginoplasty may have a reduced sensitivity to local estrogen therapy due to decrease of estrogen receptors expression in the vaginal mucosa.

Immunohistochemical localization of androgen and progesterone receptors in the uterus of the camel (Camelus dromedarius)

Ten adult, cyclic female camels (Camelus dromedarius) were used to describe the distribution of androgen (AR) and progesterone (PR) receptors in the uterus using immunohistochemistry. Both AR and PR were distributed throughout the different compartments of the uterus with nuclear staining for AR and PR seen in the cells of epithelia (luminal and glandular), stroma and myometrial smooth muscles. AR immunostaining was not uniform in distribution and intensity; the surface epithelium and the glandular epithelium in the adluminal region of the endometrium showed lower AR immunoreactivity than other compartments of the uterus. PR immunostaining showed uniformity in both distribution and intensity strong PR immunostaining intensity in almost all cells of the different uterine compartments. The intensity and distribution of PR immunostaining in epithelia of lumen and glands in the adluminal regions of endometrium was higher (P<0.05) than that of AR. In conclusion, immunohistochemical localization of AR and PR in the uterus of the cyclic dromedary camel indicates the important roles of androgen and progesterone in controlling the uterine activity during the follicular phase.