Wilson M E, Handa R J
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USA.
J Steroid Biochem Mol Biol. 1998 Jul;66(1-2):71-8. doi: 10.1016/s0960-0760(98)00007-7.
FSH-beta mRNA is dramatically regulated in the infantile female rat anterior pituitary. Elevated plasma levels of FSH correspond with increased FSH-beta mRNA levels which peak on PND 12. The source of this regulation does not appear to be GnRH, since the administration of a potent GnRH antagonist does not suppress FSH-beta mRNA levels. Consequently, we have examined the effects of the gonadal steroid hormones, estrogen and androgen, on the maintenance of gonadotropin secretion and gene expression both in vivo and in vitro. Androgen and estrogen action was blocked in vivo with the specific receptor antagonists, flutamide (150 microg) and tamoxifen (200 microg). Administration of antagonists during two different three day time-periods of infantile life [postnatal day (PND) 8-11 and PND 11-14] resulted in differing effects on both FSH and LH secretion as well as on FSH-beta and LH-beta mRNA levels. Flutamide and tamoxifen treatment both suppressed FSH secretion at either age examined (p < 0.01). LH secretion was suppressed by both treatments but only at the younger of the two ages (p < 0.01). In contrast to its effects on FSH secretion, tamoxifen suppressed FSH-beta mRNA levels in the later group only. LH-beta mRNA levels were suppressed by tamoxifen, but only in the younger age group (p < 0.05). The direct effects of steroid hormones on infantile pituitary gonadotrophs were examined in vitro by incubating cells with dihydrotestosterone propionate (DHTP; 10(-8) M) or 17beta-estradiol (E; 10(-8) M). Both DHT and E treatment stimulated FSH secretion when measured 48 h later (p < 0.01). There were no effects on LH secretion. FSH-beta mRNA levels were also stimulated by DHT at 48 h (p < 0.01). Estradiol treatment transiently increased FSH-beta mRNA levels at 2 and 6 h following treatment (p < 0.01) but not at 48 h. LH-beta levels were suppressed by DHT treatment (p < 0.05), and E transiently elevated LH-beta mRNA levels at 2 h (p < 0.05). Taken together these studies indicate that gonadotrophs from infantile female rats are capable of responding directly to steroid hormones, and may play a role in the selective stimulation of FSH secretion and expression in vivo.
促卵泡激素β亚基（FSH-β）信使核糖核酸（mRNA）在幼年雌性大鼠的垂体前叶中受到显著调控。促卵泡激素（FSH）血浆水平升高与FSH-β mRNA水平增加相对应，在出生后第12天（PND 12）达到峰值。这种调控的来源似乎不是促性腺激素释放激素（GnRH），因为给予强效GnRH拮抗剂并不会抑制FSH-β mRNA水平。因此，我们研究了性腺甾体激素，即雌激素和雄激素，在体内和体外对促性腺激素分泌和基因表达维持的影响。在体内用特异性受体拮抗剂氟他胺（150微克）和他莫昔芬（200微克）阻断雄激素和雌激素的作用。在幼年生活的两个不同的三天时间段[出生后第（PND）8 - 11天和PND 11 - 14天]给予拮抗剂，对FSH和LH分泌以及FSH-β和LH-β mRNA水平产生了不同的影响。氟他胺和他莫昔芬治疗在两个检测年龄中的任何一个都抑制了FSH分泌（p < 0.01）。两种治疗都抑制了LH分泌，但仅在两个年龄中较小的那个年龄（p < 0.01）。与其对FSH分泌的影响相反，他莫昔芬仅在较晚的组中抑制FSH-β mRNA水平。他莫昔芬抑制了LH-β mRNA水平，但仅在较年轻的年龄组中（p < 0.05）。通过用丙酸二氢睾酮（DHTP；10⁻⁸ M）或17β-雌二醇（E；10⁻⁸ M）孵育细胞，在体外研究了甾体激素对幼年垂体促性腺细胞的直接作用。48小时后测量时，DHT和E处理均刺激了FSH分泌（p < 0.01）。对LH分泌没有影响。48小时时，DHT也刺激了FSH-β mRNA水平（p < 0.01）。雌二醇处理在处理后2小时和6小时短暂增加了FSH-β mRNA水平（p < 0.01），但在48小时时没有增加。DHT处理抑制了LH-β水平（p < 0.05），而E在2小时时短暂升高了LH-β mRNA水平（p < 0.05）。综合这些研究表明，幼年雌性大鼠的促性腺细胞能够直接对甾体激素作出反应，并且可能在体内对FSH分泌和表达的选择性刺激中发挥作用。
