Perel E, Daniilescu D, Kindler S, Kharlip L, Killinger D W
J Clin Endocrinol Metab. 1986 Feb;62(2):314-8. doi: 10.1210/jcem-62-2-314.
The present study was designed to determine if stromal cells derived from human breast adipose tissue contain 5 alpha-reductase activity, and to study the effect of 5 alpha-reduced androgens on aromatase activity under basal and cortisol stimulated conditions. Stromal cells were prepared from breast adipose tissue obtained at the time of surgery from four patients. The cells were isolated after collagenase digestion and were cultured in alpha-minimum essential medium with 15% fetal calf serum. Studies were carried out between days 4 and 11 of the third subculture in the presence or absence of cortisol (10(-6) M). Metabolism of androstenedione (A) was studied over a period of 8 h after addition of medium containing 20 X 10(6) dpm (100 pM) [3H]A. The cells metabolized A to estrone (E1), testosterone (T), 5 alpha-androstane 3, 17-dione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone. On day 7 of culture, product formation expressed as percent conversion of A per 1 X 10(6) cells ranged as follows: E1, 0.02-0.13; T, 0.12-0.36; 5 alpha-A-dione, 2.05-9.91; and a fraction containing AND and dihydrotestosterone, 0.38-0.59. In the presence of cortisol the rate of cell growth was decreased by 25% to 50%. The formation of E1 increased 150- to 1500-fold and AND formation increased 2- to 8-fold. There was no consistent change in the formation of 5 alpha-A-dione and T. The addition of 5 alpha-A-dione (10(-6) M) to the culture medium at the time of assay resulted in greater than 90% inhibition of E1 formation under both basal and cortisol stimulated conditions. The studies indicate that adipose tissue is an important site for the formation of 5 alpha-reduced androgens.
本研究旨在确定源自人乳腺脂肪组织的基质细胞是否含有5α-还原酶活性，并研究在基础和皮质醇刺激条件下5α-还原雄激素对芳香化酶活性的影响。基质细胞取自4例患者手术时获取的乳腺脂肪组织。细胞经胶原酶消化后分离，在含15%胎牛血清的α-最低必需培养基中培养。在第三次传代培养的第4至11天，在有或无皮质醇（10(-6) M）的情况下进行研究。在加入含20×10(6) dpm（100 pM）[3H]雄烯二酮（A）的培养基后，对雄烯二酮（A）的代谢进行了8小时的研究。细胞将A代谢为雌酮（E1）、睾酮（T）、5α-雄烷-3,17-二酮（5α-A-二酮）、雄甾酮（AND）和双氢睾酮。在培养的第7天，以每1×10(6)个细胞中A的转化率百分比表示的产物形成情况如下：E1，0.02 - 0.13；T，0.12 - 0.36；5α-A-二酮，2.05 - 9.91；以及含有AND和双氢睾酮的部分，0.38 - 0.59。在有皮质醇的情况下，细胞生长速率降低了25%至50%。E1的形成增加了150至1500倍，AND的形成增加了2至8倍。5α-A-二酮和T的形成没有一致的变化。在测定时向培养基中添加5α-A-二酮（10(-6) M），在基础和皮质醇刺激条件下均导致E1形成的抑制率大于90%。这些研究表明脂肪组织是5α-还原雄激素形成的重要部位。
