• Clinical and Experimental Reproductive Medicine
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• 제32권4호
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• pp.325-330
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• 2005

Objective: To investigate the histologic features of the uterus and adnexae extirpated from gender identity disorder (GID) patients that received depot androgen injection. Methods: We reviewed the histologic findings of the uterus and adnexae removed from sixteen GID patients, who had taken depot androgen injection for 5~168 months. Results: Fourteen patients (87.5%) showed the atrophied epithelium of exocervix and all of 16 patients (100%) showed the atrophy of endometrium. Seven patients (43.7%) showed multiple cystic follicles in the ovarian cortex and 6 patients (37.5%), 3 patients (18.7%) showed corpus albicans and corpus luteum, respectively. Conclusions: Exogenous androgen induced atrophy of cervix and endometrium. This effect was more prominent in the endometrium. In addition, PCO-like histologic features were observed in the ovary.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6615-6619
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• 2015

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.441-448
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• 2017

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

• 한국발생생물학회지:발생과생식
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• 제22권1호
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• pp.19-27
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• 2018

In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection.

• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.220-225
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• 2018

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent $M{\ddot{u}}llerian$ duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

• Natural Product Sciences
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• 제29권1호
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• pp.31-37
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• 2023

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

• 동의생리병리학회지
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• 제18권3호
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• pp.863-867
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• 2004

Herba Patriniae(HP) has been known to exert anti-inflammation and -tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that HP extract induced apoptosis in androgen-dependent prostate cancer LNCaP cells as evidenced by DNA fragmentation. Our data demonstrated that HP extract-induced apoptotic cell death was accompanied by inhibition of NF- κB activation, lowering effects of intracellular prostate specific antigen(PSA) and androgen reoeptor(AR) expression in a time dependent manner. Taken together, HP extract may inhibit the proliferation of prostate cancer LNCaP cell associated with inhibition of NF- κB activation, PSA and AR expression and that of apoptosis.

• BMB Reports
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• 제47권11호
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• pp.643-648
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• 2014

Stanniocalcin (STC), a glycoprotein hormone originally discovered in fish, has been implicated in calcium and phosphate homeostasis. While fishes and mammals possess two STC homologs (STC1 and STC2), the physiological roles of STC2 are largely unknown compared with those of STC1. In this study, we identified Ran-binding protein M (RanBPM) as a novel binding partner of STC2 using yeast two-hybrid screening. The interaction between STC2 and RanBPM was confirmed in mammalian cells by immunoprecipitation. STC2 enhanced the RanBPM-mediated transactivation of liganded androgen receptor (AR), but not thyroid receptor ${\beta}$, glucocorticoid receptor, or estrogen receptor ${\beta}$. We also found that AR interacted with RanBPM in both the absence and presence of testosterone (T). Furthermore, we discovered that STC2 recruits RanBPM/AR complex in T-dependent manner. Taken together, our findings suggest that STC2 is a novel RanBPM-interacting protein that promotes AR transactivation.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.62-70
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• 2006

전립선비대증은 노인 남성에서 흔히 유발되는 질환이며, 노화가 진행될 수록 빈도가 높아지는 특징을 가진다. 이 질환의 원인은 전립선 기질세포의 과도한 증식으로 유발된다고 알려져 있지만 그 자세한 기전에 대해서는 잘 알려져 있지 않다. 전립선비대증에서 progesterone 수용체 양성 세포가 다른 전립선 종양에 비해서 많고, progesterone은 testosterone에서 DHT로 전환되는 것을 감소시키는 역할을 가진다고 알려졌다. 또한 남성 전립선 평활근의 과증식에 의한 질환이므로 평활근 세포의 증식과 관련성이 있다고 보고된 COX-2의 전립선비대증에 대한 영향에 대한 연구가 필요하다. 전립선 기질세포에 progesterone을 3일간 투여하여 배양한 경우 기질세포 증식은 차이가 없었다. Progesterone을 단독 또는 DHT와 같이 투여한 기질세포에서 남성호르몬 수용체 mRNA 발현은 비처리군과 비교하여 유의한 차이가 없었다. 또한 progesterone과 DHT 동시 투여에 의한 COX-2 mRNA 발현에도 차이가 없었다. 그러나 progesterone에 의한 남성호르몬 수용체와 COX-2 단백 발현에서는 대조군과 비교하여 유의하게 감소시켰다. 이상의 결과는 progesterone은 남성호르몬 수용체에 대해 전사 후 반응 (post-transcriptional response)에 효과를 나타내어 남성호르몬 수용체 발현을 감소시키는 작용은 가지며, COX-2 발현 억제효과를 나타내므로 전립선비대증의 치료에 이용될 수 있을 것으로 사료된다.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 1996년도 춘계 학술대회
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• pp.34-39
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• 1996