Keeney D S, Mendis-Handagama S M, Zirkin B R, Ewing L L
Department of Population Dynamics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Endocrinology. 1988 Dec;123(6):2906-15. doi: 10.1210/endo-123-6-2906.
Leydig cells atrophy, losing cytoplasmic volume and the capacity for testosterone secretion, within 1-2 weeks of LH deprivation. We investigated the effects of long term (0-16 weeks) LH deprivation on the volume of an average Leydig cell, the volume of Leydig cells per testis, the number of Leydig cells per testis, and testosterone secretion by in vitro perfused testes. Endogenous LH was suppressed in adult rats by testosterone/estradiol-filled (TE) Silastic implants. The presence of Leydig cells in testes was verified by 1) morphological examination using light and electron microscopy, 2) histochemical localization of 3 beta-hydroxysteroid dehydrogenase activity (3 beta HSD), and 3) conversion of pregnenolone to progesterone by in vitro perfused testes. Marked quantitative differences existed in Leydig cell morphology among control and treated rats. The volume of an average Leydig cell and the total volume of Leydig cells per testis decreased (P less than 0.01) rapidly and progressively after TE implantation. At 16 weeks, the average Leydig cell lost 90% of its cytoplasmic volume and 65% of its nuclear volume. Analysis of variance failed to detect a significant decline in Leydig cell number per testis, despite a 16% reduction from the value in control rats (22.2 +/- 1.5 x 10(6)) in rats treated for 16 weeks (18.7 +/- 1.5 x 10(6)). After TE implantation, LH-stimulated testosterone secretion by in vitro perfused testes diminished (P less than 0.01) rapidly to 5% of the control values at 1 week and less than 0.3% of the control value from 4-16 weeks. In contrast, 25% of 3 beta HSD activity was retained (P less than 0.01 vs. controls) at 16 weeks, based on the rate of pregnenolone conversion to progesterone. Moreover, testes of treated rats secreted progesterone at a rate twice that of controls, when the steroid secretion rates were expressed per volume of Leydig cell cytoplasm. Loss of the testosterone-secreting capacity of testes after LH withdrawal was associated with a loss in the volume, but not a significant loss in the number, of Leydig cells. Thus, LH was required to maintain the differentiated structure and function of Leydig cells, but was not required to maintain the overwhelming majority of Leydig cells in the adult rat testis through 16 weeks. Moreover, at least one steroidogenic enzyme, 3 beta HSD, was retained by Leydig cells after long term LH deprivation.
在促黄体生成素(LH)缺乏的1 - 2周内,睾丸间质细胞会发生萎缩,细胞质体积减小,睾酮分泌能力丧失。我们研究了长期(0 - 16周)LH缺乏对平均间质细胞体积、每个睾丸间质细胞体积、每个睾丸间质细胞数量以及体外灌注睾丸睾酮分泌的影响。通过植入填充睾酮/雌二醇(TE)的硅橡胶管抑制成年大鼠体内的内源性LH。通过以下方法验证睾丸中是否存在间质细胞:1)利用光镜和电镜进行形态学检查;2)3β - 羟基类固醇脱氢酶活性(3βHSD)的组织化学定位;3)体外灌注睾丸将孕烯醇酮转化为孕酮。对照大鼠和处理大鼠的间质细胞形态存在明显的数量差异。TE植入后,平均间质细胞体积和每个睾丸间质细胞的总体积迅速且逐渐减小(P < 0.01)。在16周时,平均间质细胞的细胞质体积减少了90%,核体积减少了65%。方差分析未检测到每个睾丸间质细胞数量有显著下降,尽管在接受16周处理的大鼠中,间质细胞数量比对照大鼠的值(22.2 ± 1.5×10⁶)减少了16%(18.7 ± 1.5×10⁶)。TE植入后,体外灌注睾丸经LH刺激后的睾酮分泌迅速减少(P < 0.01),在1周时降至对照值的5%,在4 - 16周时低于对照值的0.3%。相比之下,基于孕烯醇酮转化为孕酮的速率,在16周时3βHSD活性保留了25%(与对照相比P < 0.01)。此外,当按间质细胞细胞质体积计算类固醇分泌速率时,处理大鼠的睾丸分泌孕酮的速率是对照大鼠的两倍。LH撤除后睾丸睾酮分泌能力的丧失与间质细胞体积的减小有关,但间质细胞数量没有显著减少。因此,LH是维持间质细胞分化结构和功能所必需的,但在成年大鼠睾丸中,在长达16周的时间里,维持绝大多数间质细胞并不需要LH。此外,长期LH缺乏后,间质细胞至少保留了一种类固醇生成酶,即3βHSD。