Campbell B K, Gordon B M, Scaramuzzi R J
CSIRO Division of Animal Production, New South Wales, Australia.
J Endocrinol. 1994 Oct;143(1):13-24. doi: 10.1677/joe.0.1430013.
Transforming growth factor alpha (TGF alpha) inhibits hormone production by cultured follicular cells but evidence of an effect of TGF alpha on ovarian hormone secretion in vivo is still required. Eleven ewes with an autotransplanted ovary received, by ovarian arterial infusion, either 5 micrograms/h recombinant rat TGF alpha (n = 6) or placebo (n = 5) for 12 h on day 10 of the luteal phase. Two hours before the start and 1 hour before the end of the infusion each ewe received a single injection of gonadotrophin-releasing hormone (GnRH; 150 ng i.v.). Two hours after the end of the infusion luteal regression was induced with prostaglandin F2 alpha (PGF2 alpha; 125 micrograms i.m.). Ovarian and jugular venous blood samples were taken at 10-min, 15-min or 4-h intervals from 2 h before the start of the infusion until 96 h after PGF2 alpha and the rates of secretion of ovarian oestradiol, inhibin, progesterone and androstenedione were determined. Jugular venous concentrations of LH and FSH were also measured and follicle populations monitored by real-time ultrasound scanning. Infusion of TGF alpha resulted in a significant (P < 0.05) depression in the amplitude of the pulsatile response of oestradiol and androstenedione secretion to the GnRH-induced LH pulse at the end of the infusion. Ovarian inhibin secretion was acutely suppressed by TGF alpha infusion (P < 0.001) and remained lower than controls for the period of the experiment. Luteal phase progesterone secretion was also acutely inhibited (P < 0.001) by infusion of TGF alpha, and in one treated ewe progesterone secretion was elevated 48-84 h after PGF2 alpha. Jugular venous concentrations of FSH in TGF alpha-treated ewes were significantly (P < 0.001) elevated over controls during the first 48 h of the follicular phase and the LH surge was delayed for about 10 h (P < 0.05). Infusion of TGF alpha caused a marked decline (P < 0.05) in the number of large follicles within 12 h of the end of the infusion. Two of the six treated ewes, including the one with high follicular phase progesterone, had unusually large (8.7 and 10 mm) follicles present from 48-96 h after PGF2 alpha. We conclude that direct arterial infusion of TGF alpha results in acute inhibition of ovarian steroid and inhibin secretion that is associated with induction of atresia in the population of large follicles. The lack of feedback of ovarian hormones results in a rebound increase of FSH which stimulates the growth of more ovarian follicles and the eventual re-establishment of ovarian hormone secretion and normal cyclicity.
转化生长因子α（TGFα）可抑制培养的卵泡细胞产生激素，但TGFα对体内卵巢激素分泌影响的证据仍有待证实。11只自体移植卵巢的母羊在黄体期第10天通过卵巢动脉输注，以每小时5微克的速度接受重组大鼠TGFα（n = 6）或安慰剂（n = 5），持续12小时。在输注开始前2小时和结束前1小时，每只母羊接受一次促性腺激素释放激素（GnRH；150纳克静脉注射）注射。输注结束后2小时，用前列腺素F2α（PGF2α；125微克肌肉注射）诱导黄体退化。从输注开始前2小时到PGF2α注射后96小时，每隔10分钟、15分钟或4小时采集卵巢和颈静脉血样，测定卵巢雌二醇、抑制素、孕酮和雄烯二酮的分泌率。同时测量颈静脉中LH和FSH的浓度，并通过实时超声扫描监测卵泡数量。输注TGFα导致输注结束时雌二醇和雄烯二酮分泌对GnRH诱导的LH脉冲的脉动反应幅度显著降低（P < 0.05）。TGFα输注可急性抑制卵巢抑制素分泌（P < 0.001），并在实验期间一直低于对照组。黄体期孕酮分泌也因TGFα输注而急性受到抑制（P < 0.001），在一只接受治疗的母羊中，PGF2α注射后48 - 84小时孕酮分泌升高。在卵泡期的前48小时，接受TGFα治疗的母羊颈静脉中FSH浓度显著高于对照组（P < 0.001），LH峰延迟约10小时（P < 0.05）。输注TGFα导致输注结束后12小时内大卵泡数量显著减少（P < 0.05）。6只接受治疗的母羊中有2只，包括卵泡期孕酮水平高的那只，在PGF2α注射后48 - 96小时出现异常大的卵泡（8.7和10毫米）。我们得出结论，直接动脉输注TGFα可急性抑制卵巢类固醇和抑制素分泌，这与大卵泡群体闭锁的诱导有关。卵巢激素反馈的缺乏导致FSH反弹增加，刺激更多卵巢卵泡生长，最终重新建立卵巢激素分泌和正常的周期性。
