Lesley A Nolan

Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment

We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066±0.016% and 0.030±0.012% (mean±SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261±0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 μm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis — identified as classical apoptotic bodies — is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60–70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.

The effects of age and spontaneous adenoma formation on trophic activity in the rat pituitary gland: a comparison with trophic activity in the human pituitary and in human pituitary adenomas.

The effects of ageing on trophic activity in the pituitary gland and the molecular events that underlie pituitary tumour formation are poorly understood. In the present study we have used an extremely accurate system to analyse trophic activity in human pituitary tumours and compared our findings with trophic activity in spontaneous rat pituitary adenomas and with changes in basal rates of turnover as the animals age. Thin, hematoxylin and eosin‐stained pituitary sections from groups of male Wistar rats aged 6 weeks to 16 months, killed at 90‐min intervals after receiving a single intraperitoneal bolus of colchicine to block cellular passage through mitosis, were evaluated histologically. Extremely accurate quantification of small changes in the prevalence of trophic events, and thus the rate of cell turnover, was achieved using a dedicated computerized aid to manual cell counting. Results were compared with the prevalence of mitotic activity in 24 spontaneous rat pituitary adenomas and with a series of 97 archival human pituitary adenomas and 24 normal human pituitary glands obtained at autopsy. In rats, average basal pituitary cell turnover declined by over 95% between 6 weeks and 16 months of age. Concurrent with this decline was a marked increase in the prevalence of adenoma formation. The prevalence of mitotic activity in spontaneous rat pituitary adenomas averaged almost twice that seen in normal, young rat pituitary and exceeded 16 times that seen in the pituitary of aged animals. In contrast, when compared to normal human pituitary tissue, average trophic activity in human pituitary adenomas remained extremely low.

Chronic Iodine Deprivation Attenuates Stress‐Induced and Diurnal Variation in Corticosterone Secretion in Female Wistar Rats

Many millions of people throughout the world are at risk of developing iodine deficiency‐associated disorders. The underlying effects of iodine deficiency on neuroendocrine function are poorly defined. We have studied stress‐induced and diurnal variation in corticosterone secretion in female rats rendered chronically hypothyroid by feeding them an iodine‐free diet for 6 months. Corticosterone secretory responses in iodine deficient animals were compared to those seen in animals rendered hypothyroid with propylthiouracil and untreated controls. By using a well‐validated, automated blood sampling system to collect small samples of blood over the complete daily cycle in unrestrained animals, we have demonstrated for the first time that the normal diurnal rhythm of corticosterone secretion is lost in chronic iodine deficiency and that the corticosterone secretory response to the psychological stress of 10 min exposure to white noise is attenuated. Despite restoration of circulating triiodothyronine and thyrotropin releasing hormone‐ and thyroid stimulating hormoneβ‐transcript prevalence in the hypothalamus and pituitary, respectively, 1 month after restoration of normal iodine‐containing diet both the diurnal variation in corticosterone levels and the corticosterone secretory response to the noise stress remained reduced in amplitude compared to control animals. Thus, chronic hypothyroidism induced by iodine deficiency significantly attenuates hypothalamo‐pituitary‐adrenal axis activity, an effect that persists after functional recovery of the thyroid axis.