The characterisation of oestrogen receptors by gel filtration in hormone-sensitive tissues: immature rat uterus, brain and thymus

The aims of this project were to investigate the binding characteristics of the cytosolic oestrogen receptor in the uterus, brain and thymus of immature Wistar rats. The specificities of the receptor in the uterus are well established. The specificities of the cytosolic receptor in the uterus and thymus of immature female Wistar rats were tested against a range of steroids and the values found for the thymus compared with those for the uterus. The concentrations and dissociation constant (Kd) of the cytosolic oestrogen receptor were determined in uterus, brain and thymus of male and female rats at 5,18 and 30 days of age. Clomiphene citrate (CC), an oestrogen antagonist/partial agonist, oestradiol (E2), CC+E2 or 4-hydroxyandrostenedione (4-OHA), an aromatase inhibitor, were administered to animals at 15 days in order to study the effects of these compounds on receptor binding characteristics at 30 days. Significant differences in specificity were found between the thymus and uterus, the cytosolic oestrogen receptor in the thymus exhibited significantly higher affinity for corticosterone than it did in the uterus. Male animals were heavier than females at 30 days. Uterus and thymus weights increased exponentially between 5 and 30 days. The tissue-to-body weight ratio increased in uterus between 18 and 30 days and increased in the thymus in both sexes between 5 and 18 days. In males at 30 days, the tissue-to-body weight ratio of the thymus was significantly lower than in females of the same age. Cytosolic oestrogen receptor concentrations in the uterus, brain and thymus differed between some age and/or sex groups. Cytosolic oestrogen receptor concentrations increased exponentially in the uterus between the different age groups. Cytosolic oestrogen receptor concentrations in both thymus and hypothalamus at 5 days were significantly higher in females than in males of the same age group. No differences in cytosolic oestrogen receptor concentrations were found between the sexes in the cortex at 5 and 18 days but at 30 days, receptors were not detectable in this brain area. The Kd for moxestrol, a synthetic oestrogen agonist that is not bound by alphafetoprotein present in the blood of immature rats, was similar in all tissues. E2 and CC+E2 treatments resulted in decreased body and thymus weight in both sexes, increased uterus weight and decreased thymus weight in both sexes but led to increased uterus weight. CC treatment decreased the concentration of the receptors in the female thymus only; E2 and CC+E2 treatments decreased the concentratIon of the receptor to levels that were undetectable in hypothalamus and thymus in both sexes, 4-OHA treatment increased thymus weight and cytosolic receptor concentrations in the hypothalamus and thymus of males only. These results suggest that cytosolic oestrogen receptors in uterus, brain and thymus are similar and that sex differences in these tissues are mediated by differential exposure to oestradiol during the early postnatal period. The thymus is crucial to the development of the immune response. The finding that the cytosolic oestrogen receptor differed from the uterus receptor in its affinity for corticosterone and that sex differences in cytosolic oestrogen receptor concentrations were present in the thymus at 5 days could be relevant to the sex dimorphisms that exist in autoirnmune disease manifestation

Development of targeted viral vectors for cardiovascular gene therapy

No abstract available