Gräf K J, Horowski R, Etreby M F
Acta Endocrinol (Copenh). 1977 Jun;85(2):267-78. doi: 10.1530/acta.0.0850267.
The purpose of the present study was to investigate the biological effectiveness of two highly potent prolactin (PRL) inhibitors, lisuride hydrogen maleate (LMH) and 2-Br-alpha-ergocryptine (CB-154), in the absence of hypothalamic factors acting directly at the level of the anterior pituitary. Hypophysectomized female rats bearing 4 transplanted pituitaries beneath the kidney capsules were treated with oestradiol benzoate (OeB) and progesterone (P) with or without simultaneous administration of LHM or CB-154 for 22 days in order stimulate or inhibit lobula-alveolar growth of the mammary glands. In addition to the investigation of the mammary glands by DNA determination and assessment of the histological pictures, the aim of this study was directed towards the influence of the substances tested at the level of the anterior pituitary remote from the hypothalmus. In this connection the changes in the different cells within the ectopic pituitaries as revealed by immunoenzyme-cytochemical studies were investigated. The results obtained support the classical view of a neuroendocrine regulation of mammary gland growth and the importance of oestrogens, P and PRL within this system. Both ergot derivatives LHM and CB-154 were able to antagonize the stimulatory effect of OeB combined with P on the mammary gland. With regard to the mechanism of action of LHM and CB-154 it is concluded that both substances act via a direct action on dopaminergic receptors within the ectopic anterior pituitary.
本研究的目的是在没有直接作用于垂体前叶水平的下丘脑因子的情况下,研究两种高效催乳素(PRL)抑制剂马来酸麦角乙脲(LMH)和2-溴-α-麦角隐亭(CB-154)的生物学效应。将垂体移植到肾囊下的4个垂体的去垂体雌性大鼠,用苯甲酸雌二醇(OeB)和孕酮(P)治疗,同时给予或不给予LMH或CB-154,持续22天,以刺激或抑制乳腺小叶-腺泡的生长。除了通过DNA测定和组织学图片评估来研究乳腺外,本研究的目的还在于测试物质对远离下丘脑的垂体前叶水平的影响。在此方面,研究了免疫酶细胞化学研究揭示的异位垂体内不同细胞的变化。所获得的结果支持了乳腺生长神经内分泌调节的经典观点以及雌激素、P和PRL在该系统中的重要性。两种麦角衍生物LMH和CB-154都能够拮抗OeB与P联合对乳腺的刺激作用。关于LMH和CB-154的作用机制,可以得出结论,这两种物质都是通过直接作用于异位垂体前叶内的多巴胺能受体而起作用的。