Development and characterization of a novel rat model of estrogen-induced mammary cancer

The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is highly relevant for use in establishing the endocrine, genetic, and environmental bases of breast cancer etiology and identifying novel agents and strategies for preventing breast cancer. E2 treatment rapidly induces mammary cancer in female ACI rats and simultaneously induces pituitary lactotroph hyperplasia and adenoma. The pituitary tumors can result in undesired morbidity, which compromises long-term studies focused on mammary cancer etiology and prevention. We have defined the genetic bases of susceptibility to E2-induced mammary cancers and pituitary tumors and have utilized the knowledge gained in these studies to develop a novel inbred rat strain, designated ACWi, that retains the high degree of susceptibility to E2-induced mammary cancer exhibited by ACI rats, but lacks the treatment-related morbidity associated with pituitary lactotroph hyperplasia/adenoma. When treated with E2, female ACWi rats developed palpable mammary cancer at a median latency of 116 days, an incidence of 100% by 161 days and exhibited an average of 15.6 mammary tumors per rat following 196 days of treatment. These parameters did not differ from those observed for contemporaneously treated ACI rats. None of the E2-treated ACWi rats were killed before the intended experimental end point due to any treatment-related morbidity other than mammary cancer burden, whereas 20% of contemporaneously treated ACI rats exhibited treatment-related morbidity that necessitated premature killing. The ACWi rat strain is well suited for use by those in the research community, focusing on breast cancer etiology and prevention.

Photoperiodic regulation of prolactin secretion: changes in intra-pituitary signalling and lactotroph heterogeneity

Many mammalian species utilise day-length (photoperiod) to adapt their physiology to seasonal changes in environmental conditions, via secretion of pineal melatonin. Photoperiodic regulation of prolactin secretion is believed to occur via melatonin-mediated changes in the secretion of a putative prolactin secretagogue, tuberalin, from the pituitary pars tuberalis. Despite the in vivo and in vitro evidence in support of this intra-pituitary signalling mechanism, the identity of tuberalin has yet to be elucidated. This paper reviews recent advances in the characterisation of tuberalin and the regulation of its secretion. Furthermore, the hypothesis that pituitary lactotroph cells display heterogeneity in their response to changing photoperiod and tuberalin secretion is examined.