Two women who had previously undergone pituitary stalk transection for cancer of the breast provided a unique modei to test whether in human subjects TRH stimulates PRL release by direct action on the pituitary or by some secondary mechanism at the hypothalamic level. The completeness of stalk section was thoroughly documented in both patients. The intravenous administration of synthetic TRH caused a significant, though delayed, rise in PRL levels. Chlorpromazine, which induces PRL secretion by an effect on the hypothalamus, did not affect.PRL levels. Thus, in human beings, TRH appears to stimulate PRL release by a direct action on the pituitary. (/ Clin Endocrinol Metab 39: 1148, 1974 A LTHOUGH the weight of evidence favors l \ the hypothesis that TRH acts directly at the pituitary level to cause the release of prolactin (PRL), contradictory animal studies have been reported, possibly due to interspecies variation and differences in experimental methodology. The release of TSH from pituitary organ cultures following TRH stimulation has been observed in many species (1-3); however, the in vitro release of PRL in response to TRH has proven more difficult to demonstrate. For this reason, some question remains whether the highly reproducible in vivo release of PRL in response to exogenous TRH in man (4,5) might not occur through some indirect mechanism. To study this question, we have measured the TSH and PRL responses to the administration of TRH in 2 women who had previously undergone pituitary stalk section for metastatic cancer of the breast.A.S., a 63-year-old woman, had a right mastectomy for cancer of the breast in 1952. In 1958, because of pulmonary metastases and intractable pleural effusions, she had a pituitary stalk section with insertion of a tantalum plate above the sellar diaphragm. Her metastases subsequently resolved and have not recurred. Following stalk section, she developed thyroid and adrenocortical insufficiency which were treated with cortisone and L-thyroxine. The latter hormone was discontinued 2 weeks prior to these studies. On repeated testing, she had no detectable plasma growth hormone response to insulin-induced hypoglycemia and urinary gonadotropins have been absent by bioassay. Physical examination revealed no evidence of recurrent metastatic disease. Routine lab studies were normal and plasma thyroxine iodine (TJ) by competitive binding was 0.3 /ug/100 ml (nl 2.9-7.5 fig/100 ml).C.H., a 72-yr-old woman, had a left mastectomy for cancer of the breast in 1956. In 1966, because of multiple skin metastases, she had an oophorectomy and was subsequently given testosterone, then diethylstilbesterol. In December 1966, she had a pituitary stalk section with insertion of a tantalum plate. She likewise developed adrenal and thyroid insufficiency and exhibited no GH responses to insulin hypoglycemia. Her urinary gonadotropins which were high preoperatively fell to low levels postoperatively. Serum LH was undetectable by radioimmunoassay. She has been maintained on replacement dosages of cortis...
