Spontaneous pituitary tumorigenesis and plasma oestradiol in ageing female C57BL/6J mice

Macroscopic pituitary tumours occur with increasing frequency in ageing female C57BL/6J mice. Tumour incidence rises steadily between 14 and 30 months from 6 to 61%. Two stepwise increments in pituitary weight, indicative of hyperplasia, occur prior to the appearance of tumours. The first, at 5 months, coincides with the onset of regular estrous cyclicity, and hence maximal exposure to plasma oestradiol (E₂). Average plasma E₂ concentration in cycling mice is 15.4 pg/ml ± 1.73 SE. The second increment, at 14 months, coincides with the first appearance of tumours and with the onset of cycle irregularity, which is characterized by persistent vaginal cornification and a 50% reduction in exposure to E₂. Although exogenous E₂ can induce pituitary tumours, its reduced concentration during the initial phase of tumorigenesis suggests that altered sensitivity or other factors are involved.