The initial results of combined therapy are promising. Although preoperative XRT was very well tolerated, BT to the upper abdomen was associated with substantial toxicity. Our current protocol includes selective application of BT to the lower abdomen only.

Lactotrophs have several different kinds of receptors, such as dopaminergic D₂, somatostatin, angiotensin II and thyrotropin-releasing hormone receptors, which stimulate or inhibit prolaction release. We have studied the specificity of phenoxybenzamine on receptors in lactotrophs. Phenoxybenzamine is a β-haloalkylamine which alkylates chemically active radicals such as hydroxy, sulfhydryl, and amino groups. This alkylation is an irreversible chemical reaction in contrast to the receptor-secretagogue complex which is present in a state of dynamic equilibrium. Primary cultured rat adenohypophyseal cells were used in this study. A dose-response relationship was examined between concentrations of phenoxybenzamine pretreatment and prolactin release using a monolayer cell culture system. The inhibitory action of dopamine (10 µmol/l) on the control group (13.0 ± 0.1 ng/ml or 86% inhibition relative to the control) was significantly higher than on the 0.1-µmol/l phenoxybenzamine-pretreated group (39.0 ± 0.2 ng/ml or 58% inhibition relative to the control), but the stimulatory effect of thyrotropin-releasing hormone on prolactin release was not significantly affected up to a 10-µmol/l phenoxybenzamine pretreatement as compared with the control group. We thus selected a phenoxybenzamine concentration of 0.1 µmol/l for the next series of perifusion experiments in order to examine dynamic changes in prolactin release. The basal prolaction release was decreased to almost half by phenoxybenzamine pretreatment. The inhibitory action of dopamine (0.1 µmol/l containing 0.1 mmol/l ascorbic acid) was significantly less in the phenoxybenzamine-pretreated group (68% of the basal prolactin concentration) than in the control group (31% of the basal concentration). However, the relative actions of somatostatin, thyrotropin-releasing hormone, angiotensin II, and dibutyryl adenosine 3’,5’-cyclic adenosine monophosphate were not significantly affected by the phenoxybenzamine pretreatment. These observations suggest that phenoxybenzamine is relatively selective to dopaminergic D₂ receptors in primary cultured lactotrophs. The basal prolactin release in the phenoxybenzamine-pretreated group increased steadily during the experimental period. The basal prolactin release was doubled within 153.7 ± 22.3 min.

The neurohypophysial hormones, oxytocin and vasopressin, are present as non-covalently bound complexes with their designated neurophysin in the secretory granules of the posterior pituitary. The neurophysins are generally considered to be biologically inert carrier proteins for oxytocin and vasopressin. We have examined the actions of bovine neurophysin-I (bNP-I), bovine neurophysin-II (bNP-II), rat neurophysin (rat NP) and oxytocin on prolactin release using primary cultured rat pituitary cells. A dynamic perifusion system was chosen to test their stimulatory actions. The rat NP and bNP-II stimulated prolactin release. It is a new observation that rat NP and bNP-II stimulate prolactin release from primary cultured rat pituitary cells. The maximum sensitivities, the lowest concentration which stimulate prolactin release, of rat NP, bNP-II, bNP-I and oxytocin in primary cultured cells were 1 nmol/1, 1 nmol/l, 1000 nmol/1 and 1 nmol/1 respectively. The maximum sensitivities of rat NP and bNP-II were within the physiologically relevant concentrations.