Zorrilla R, Simard J, Rhéaume E, Labrie F, Pelletier G
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
Neuroendocrinology. 1990 Nov;52(5):527-36. doi: 10.1159/000125639.
The influence of sex steroids as well as the possible involvement of dopaminergic pathways in the modulation of pre-pro-somatostatin (SS) mRNA levels was investigated by quantitative in situ hybridization in the hypothalamic periventricular nucleus (PeN) in adult male and female rats. In situ hybridization was performed using a [35S]-labeled cDNA probe encoding pre-proSS mRNA. Gonadectomy performed 14 days earlier decreased the mean number of silver grains/neuron corresponding to the relative pre-proSS mRNA levels by 22% in male and by 18-28% in female rats. A 14-day treatment with the nonaromatizable androgen dihydrotestosterone (DHT) increased the mean number of silver grains/neuron by 34-40% in gonadectomized animals of both sexes. Moreover, administration of 17 beta-estradiol (E2, 0.25 microgram twice daily) increased pre-proSS mRNA levels by 40% in ovariectomized (OVX) animals. Such treatment with E2 or DHT changed the frequency distribution profile of the hybridization signal intensity, thus increasing the percentage of highly labeled neurons (greater than or equal to 61 grains/neuron) by 10 to 12-fold. A 14-day treatment with the D2 dopamine receptor agonist bromocriptine (BRO) increased pre-proSS mRNA levels by 15 and 28% in intact female and OVX animals, respectively, while the dopaminergic antagonist haloperidol (HAL) decreased the value of this parameter by 20 and 30%. Furthermore, BRO increased pre-proSS mRNA levels by 10 and 20% in intact and castrated male rats, respectively, whereas HAL decreased pre-proSS mRNA levels by 25 and 14% in the same groups of animals. Administration of E2 in combination with HAL in OVX animals increased pre-proSS mRNA levels by 70% compared to those measured in OVX animals treated with HAL alone. In HAL-treated castrated male rats, administration of DHT increased the relative pre-proSS mRNA levels by 35% compared to those measured in castrated animals treated with HAL alone. The present data clearly demonstrate that androgens and estrogens as well as dopamine-mediated mechanisms could play a regulatory role in pre-proSS mRNA levels in somatostatinergic neurons in the hypothalamic PeN in both male and female rats.
采用定量原位杂交技术，研究成年雄性和雌性大鼠下丘脑室周核（PeN）中，性类固醇激素的影响以及多巴胺能通路在调节前促生长抑素（SS）mRNA水平中可能的作用机制。原位杂交使用编码前体促生长抑素mRNA的[35S]标记cDNA探针。14天前进行去势手术，使雄性大鼠中与前体促生长抑素mRNA相对水平对应的银颗粒/神经元平均数量减少22%，雌性大鼠减少18%-28%。用不可芳香化的雄激素双氢睾酮（DHT）对去势动物进行14天治疗，使两性去势动物的银颗粒/神经元平均数量增加34%-40%。此外，给去卵巢（OVX）动物每日两次注射17β-雌二醇（E2，0.25微克），可使前体促生长抑素mRNA水平增加40%。用E2或DHT进行上述治疗改变了杂交信号强度的频率分布图谱，使高标记神经元（≥61个颗粒/神经元）的百分比增加了10至12倍。用D2多巴胺受体激动剂溴隐亭（BRO）对完整雌性和OVX动物进行14天治疗，前体促生长抑素mRNA水平分别增加15%和28%，而多巴胺能拮抗剂氟哌啶醇（HAL）使该参数值分别降低20%和30%。此外，BRO使完整和去势雄性大鼠的前体促生长抑素mRNA水平分别增加10%和20%，而HAL使同组动物的前体促生长抑素mRNA水平分别降低25%和14%。在OVX动物中，E2与HAL联合给药使前体促生长抑素mRNA水平比单独用HAL治疗的OVX动物增加70%。在HAL治疗的去势雄性大鼠中，DHT给药使前体促生长抑素mRNA相对水平比单独用HAL治疗的去势动物增加35%。目前的数据清楚地表明，雄激素、雌激素以及多巴胺介导的机制可能在雄性和雌性大鼠下丘脑PeN中生长抑素能神经元的前体促生长抑素mRNA水平中发挥调节作用。
