Allan Charles M, Garcia Alvaro, Spaliviero Jenny, Zhang Fu-Ping, Jimenez Mark, Huhtaniemi Ilpo, Handelsman David J
Andrology Laboratory, ANZAC Research Institute, Concord Hospital, Sydney, Australia.
Endocrinology. 2004 Apr;145(4):1587-93. doi: 10.1210/en.2003-1164. Epub 2004 Jan 15.
Defining the gonadal effects of FSH distinct from those of LH remains difficult. We have characterized and compared the level of Sertoli and germ cell development in three mouse models recently created to isolate FSH activity from LH effects. Two models used LH-deficient hypogonadal (hpg) mice to selectively study either pituitary-independent transgenic (tg) FSH or ligand-independent activated tg FSH receptor (FSHR(+)) expression, and the third model used LH receptor (LHR)-deficient mice to isolate and examine endogenous mouse FSH effects. Stereological evaluation revealed tg-FSH or tg-FSHR(+) activity significantly increased total Sertoli cell numbers per testis in both hpg models relative to control hpg testes. Furthermore, tg-FSH dose-dependently restored hpg Sertoli cells to wild-type (wt) (non-hpg) levels, and LHR-/- testes also exhibited wt Sertoli numbers. Spermatogonial proliferation and meiotic development were enhanced by tg-FSHR(+) or tg-FSH. Despite producing normal Sertoli numbers, isolated tg-FSH activity only increased total spermatogonia and spermatocyte populations to 57 and 44% of wt, which was comparable to spermatogonia and spermatocyte numbers observed in LHR-null testes (45 and 34% of wt). Selective FSH activity initiated round spermatid formation in all three models. However, elongated spermatid formation was detected in tg-FSH and tg-FSHR(+) hpg testes but not in LHR-/- testes, which may reflect even lower intratesticular testosterone levels in LHR-null compared with hpg testes. FSH increased round and elongated spermatid numbers in hpg testes to 16 and 6% of wt without altering intratesticular testosterone levels, but failed to produce spermatozoa demonstrating the inability of FSH to complete spermatogenesis. These findings revealed that full Sertoli cell proliferation can be accomplished by FSH activity without LH requirement, and although postnatal mitotic and meiotic germ cell development can be promoted by FSH alone, LH-mediated effects remain a critical determinant for initiating the full complement of germ cells and final stages of postmeiotic development.
区分促卵泡激素（FSH）与促黄体生成素（LH）对性腺的不同作用仍然困难。我们对最近创建的三种小鼠模型中支持细胞和生殖细胞的发育水平进行了表征和比较，这些模型旨在将FSH活性与LH的作用分离。其中两种模型使用促性腺激素缺乏的性腺功能减退（hpg）小鼠，以选择性地研究垂体非依赖性转基因（tg）FSH或配体非依赖性激活的tg促卵泡激素受体（FSHR(+)）的表达，第三种模型使用促黄体生成素受体（LHR）缺陷型小鼠来分离和检测内源性小鼠FSH的作用。体视学评估显示，相对于对照hpg睾丸，在两种hpg模型中，tg-FSH或tg-FSHR(+)活性均显著增加了每个睾丸中支持细胞总数。此外，tg-FSH呈剂量依赖性地将hpg支持细胞恢复到野生型（wt）（非hpg）水平，并且LHR-/-睾丸也表现出wt支持细胞数量。tg-FSHR(+)或tg-FSH可增强精原细胞增殖和减数分裂发育。尽管产生了正常数量的支持细胞，但单独的tg-FSH活性仅使精原细胞和精母细胞总数分别增加到wt的57%和44%，这与在LHR基因敲除睾丸中观察到的精原细胞和精母细胞数量（wt的45%和34%）相当。在所有三种模型中，选择性FSH活性均启动了圆形精子细胞的形成。然而，在tg-FSH和tg-FSHR(+) hpg睾丸中检测到了长形精子细胞的形成，而在LHR-/-睾丸中未检测到，这可能反映出与hpg睾丸相比，LHR基因敲除睾丸中的睾丸内睾酮水平更低。FSH将hpg睾丸中的圆形和长形精子细胞数量增加到wt的16%和6%，而不改变睾丸内睾酮水平，但未能产生精子，这表明FSH无法完成精子发生。这些发现表明，FSH活性可在无需LH的情况下实现支持细胞的完全增殖，并且尽管FSH可单独促进出生后有丝分裂和减数分裂生殖细胞的发育，但LH介导的作用仍然是启动生殖细胞的完整补充和减数分裂后发育最终阶段的关键决定因素。
