Selman P J, van Garderen E, Mol J A, van den Ingh T S
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, University Utrecht, The Netherlands.
Vet Q. 1995 Dec;17(4):128-33. doi: 10.1080/01652176.1995.9694551.
Administration of progestins in the dog may result in overproduction of growth hormone, suppression of the hypothalamic-pituitary-adrenocortical axis, and insulin resistance. In this paper we present a comparison of the histological findings in control dogs and dogs treated with either medroxyprogesterone acetate (MPA) or proligestone (PROL). Depot preparations of MPA or PROL were administered (SC) at 3-week intervals in two groups of seven ovariohysterectomized beagle dogs, after which three dogs of each group were killed. After a 6-month period without hormone treatment during which recovery was studied, the remaining dogs received five additional injections at the same interval and were subsequently killed. Tissue samples of four intact female beagle dogs served as controls. Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA- and PROL-treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller than in control animals. In the mammary glands of progestin-treated dogs there were well developed alveoli and normal ducts adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment group had developed benign mammary tumours which varied from simple tubular and papillary adenomas to benign complex and mixed tumours, whereas no mammary tumours were observed in the control animals. In each treatment group, steroid-induced hepatopathy was observed in the liver of three dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each treatment group and was only observed after the second series of progestin administrations. Incidental findings included chronic pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pituitary gland. There were no significant differences in the frequencies of the various abnormalities between MPA- and PROL-treated dogs. Our findings correspond with the clinical and biochemical results after treatment of dogs with MPA and PROL. The high incidence of mammary tumours might be associated with our recent finding that in the dog progestins induce ectopic production of growth hormone in the mammary gland. The dog might be a good model for further studies on hormonally induced breast cancers.
给犬使用孕激素可能会导致生长激素分泌过多、下丘脑 - 垂体 - 肾上腺皮质轴受抑制以及胰岛素抵抗。在本文中，我们比较了对照犬与接受醋酸甲羟孕酮（MPA）或炔诺孕酮（PROL）治疗的犬的组织学发现。在两组各7只卵巢子宫切除的比格犬中，每隔3周皮下注射MPA或PROL的长效制剂，之后每组处死3只犬。在为期6个月的无激素治疗恢复期后研究恢复情况，其余犬以相同间隔再接受5次注射，随后处死。4只完整雌性比格犬的组织样本作为对照。孕激素治疗导致肾上腺皮质萎缩。在接受MPA和PROL治疗的犬中，束状带和网状带的总厚度均显著小于对照动物。在接受孕激素治疗的犬的乳腺中，有发育良好的腺泡以及与增生性导管上皮灶相邻的正常导管。每个治疗组中有5只犬发生了良性乳腺肿瘤，从单纯管状和乳头状腺瘤到良性复杂和混合性肿瘤不等，而对照动物中未观察到乳腺肿瘤。在每个治疗组中，3只犬的肝脏出现了类固醇诱导的肝病。每个治疗组中有2只犬出现了胰岛细胞和闰管上皮细胞空泡化，且仅在第二轮孕激素给药后才观察到。偶然发现包括慢性肾盂肾炎、非特异性皮炎和胆囊黏液发育异常。在脾脏、肺、脑或垂体的切片中未发现异常。MPA和PROL治疗的犬之间各种异常的发生率没有显著差异。我们的发现与用MPA和PROL治疗犬后的临床和生化结果相符。乳腺肿瘤的高发生率可能与我们最近的发现有关，即在犬中孕激素会诱导乳腺中生长激素的异位分泌。犬可能是进一步研究激素诱导的乳腺癌的良好模型。
