Influence of bromocriptine and oestrogen on prolactin synthesis, secretion and tumour growth in vivo in rats

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Abstract
The effects of diethylstilboestrol implants and bromocriptine administration on serum prolactin concentrations, prolactin messenger RNA (mRNA) and pituitary tumour weight were examined. Intact female Fischer 344 rats were implanted s.c. with 10 mg diethylstilboestrol (DES) under light anaesthesia. All animals except the control group carried the implant for 7 weeks at which time the rats were subdivided into five groups: A, control; B, DES for 7 weeks; C, DES for 7 weeks followed by withdrawal of DES for 1 week; D, DES for 7 weeks followed by withdrawal of DES and administration of bromocriptine for 1 week; E, DES for 8 weeks with concurrent administration of bromocriptine during the last week. Serum concentrations of prolactin were measured by radioimmunoassay, prolactin mRNA concentrations were measured by dot-blot hybridization and sodium dodecylsulphate–polyacrylamide gel electrophoresis of the in-vitro translated mRNA. Pituitary growth was estimated by changes in pituitary weight and assessed by light and electron microscopic examination. Treatment with DES dramatically increased serum prolactin concentrations and prolactin mRNA and induced pituitary tumour formation as shown by histological changes. Withdrawal of DES for 1 week did not lead to a decrease in pituitary tumour weight but was accompanied by a decrease in serum prolactin concentrations and prolactin mRNA from peak concentrations although they remained significantly increased above controls. Treatment with bromocriptine after DES implants were removed led to a significant reduction in pituitary tumour weight and a decrease in serum prolactin concentrations and prolactin mRNA. Histology of the pituitary tumour after the bromocriptine treatment showed pituitary cells similar to those from normal animals. In group E, when bromocriptine was administered in the presence of DES implants, no reduction in pituitary tumour weight occurred but serum prolactin concentrations and prolactin mRNA decreased almost to normal concentrations. Histology of the pituitary showed most cells remaining hypertrophied and similar in appearance to those seen in animals treated with DES alone. These results suggest that the mechanisms by which oestrogen and bromocriptine control prolactin synthesis and secretion are independent from those which influence pituitary tumour growth and regression. J. Endocr. (1987) 113, 383–388