Sourla A, Martel C, Labrie C, Labrie F
Medical Research Council, Centre Hospitalier de l' Université Laval Research Center and Laval University, Québec, Canada.
Endocrinology. 1998 Feb;139(2):753-64. doi: 10.1210/endo.139.2.5762.
To determine the relative role of the androgenic and/or estrogenic components of the action of dehydroepiandrosterone (DHEA) on the histomorphology and structure of the rat mammary gland, ovariectomized (OVX) female animals received DHEA administered alone or in combination with the pure antiandrogen flutamide or the pure antiestrogen EM-800 for 12 months. We have also evaluated the effect of estradiol (E2) and dihydrotestosterone constantly released from SILASTIC brand silicon implants as well as medroxyprogesterone acetate released from poly(lactide-co-glycolide) microspheres. While 1-yr OVX resulted in a severe atrophy of the mammary gland, treatment of OVX animals with DHEA stimulated lobuloalveolar and ductal growth, as well as the secretory activity of the acinar cells, thus resulting in a lobuloalveolar type of development of the mammary gland. The addition of FLU to DHEA almost completely prevented the stimulatory effect observed with DHEA alone, whereas addition of the antiestrogen EM-800 had no significant effect on the action of DHEA on the mammary gland. At the doses used, medroxyprogesterone acetate and dihydrotestosterone also stimulated ductal and alveolar development, although to a lesser degree than that achieved with DHEA. The stimulatory effect of estradiol was mainly expressed on ductal growth with a smaller stimulatory effect on lobuloalveolar development. The above-indicated stimulatory effects on lobuloalveolar development were also reflected in significant increases of the total and parenchymal gland surface areas of the mammary gland. The present study shows that androgens induce a marked lobuloalveolar type of development of the mammary gland in the rat. Moreover, these data indicate the highly predominant or almost exclusive androgenic component in the potent stimulatory action of DHEA on the histomorphology and structure of the rat mammary gland. In fact, blockade of the potential estrogenic component of DHEA action by EM-800 did not affect the stimulatory action of DHEA on mammary gland histomorphology, whereas the antiandrogen FLU almost completely blocked the effect of DHEA.
为了确定脱氢表雄酮（DHEA）作用中的雄激素和/或雌激素成分对大鼠乳腺组织形态学和结构的相对作用，对去卵巢（OVX）的雌性动物单独给予DHEA，或与纯抗雄激素氟他胺或纯抗雌激素EM - 800联合给药12个月。我们还评估了从SILASTIC品牌硅植入物持续释放的雌二醇（E2）和二氢睾酮以及从聚（丙交酯 - 乙交酯）微球释放的醋酸甲羟孕酮的作用。虽然1年的去卵巢导致乳腺严重萎缩，但用DHEA治疗去卵巢动物可刺激小叶腺泡和导管生长以及腺泡细胞的分泌活性，从而导致乳腺小叶腺泡型发育。向DHEA中添加氟他胺几乎完全阻止了单独使用DHEA时观察到的刺激作用，而添加抗雌激素EM - 800对DHEA对乳腺的作用没有显著影响。在所使用的剂量下，醋酸甲羟孕酮和二氢睾酮也刺激导管和腺泡发育，尽管程度小于DHEA。雌二醇的刺激作用主要表现在导管生长上，对小叶腺泡发育的刺激作用较小。上述对小叶腺泡发育的刺激作用也反映在乳腺总表面积和实质表面积的显著增加上。本研究表明，雄激素可诱导大鼠乳腺出现明显的小叶腺泡型发育。此外，这些数据表明，在DHEA对大鼠乳腺组织形态学和结构的强效刺激作用中，雄激素成分高度占主导或几乎是唯一的。事实上，EM - 800阻断DHEA作用中的潜在雌激素成分并不影响DHEA对乳腺组织形态学的刺激作用，而抗雄激素氟他胺几乎完全阻断了DHEA的作用。
