The effects of ovine CRF, lysine vasopressin (LVP), and their interrelationships, and rat hypothalamic extract (HME), on ACTH and beta-endorphin release by human pituitary tumor cells from two patients with Nelson's syndrome and one with Cushing's disease and on ACTH and cortisol secretion in vivo were studied. In cultured pituitary tumor cells, both LVP and CRF greatly stimulated ACTH and beta-endorphin release at maximally active concentrations of 0.1 microM and 10 nM, respectively. At these concentrations, the combination of the two substances had an additive or synergistic effect on hormone release. Low concentrations of HME potentiated and/or were synergistic with CRF-mediated ACTH release. In vivo, the combination of CRF (1 microgram/kg) and LVP (10 pressor units) induced greater ACTH release than the sum of the responses to CRF and LVP alone. This synergistic effect of CRF plus LVP concerned only ACTH release, while cortisol release after CRF plus LVP was equivalent to the sum of the maximal increments in this hormone after CRF and LVP alone. The peak levels of cortisol after a combination of CRF and LVP probably reflect the maximum stimulatory capacity of the adrenal cortex. These data support the concept that in man, both ovine CRF and vasopressin are corticotropin-releasing factors which act synergistically. Both substances might well regulate, at the pituitary level, the responsiveness of the pituitary-adrenal axis to stimuli reaching the hypothalamus. A test using ovine CRF and LVP together might provide a better index of total pituitary ACTH reserve than one using the two compounds separately.

In-vitro data of pituitary adenoma cells from 28 acromegalic patients were evaluated. In addition to GH, PRL was produced by 16 adenomas (57%) and alpha-subunit by 15 adenomas (54%) while there was a significantly higher incidence of tumours producing PRL and alpha-subunit simultaneously. From 26 pituitary adenomas enough cells were obtained in order to perform secretion studies. Percentage basal hormone release (medium: (medium + intracellular hormone)) x 100% of GH and alpha-subunit by 11 adenomas showed a close correlation while such a correlation for GH and PRL was present only in a subgroup of 10 of 13 adenomas. The responses of GH and alpha-subunit release to 10nM SMS201-995, 10nM bromocriptine, 100 nM TRH and 10nM GHRH were closely related in that a response or an absent response of GH release to the four secretagogues was virtually always attended with a response or an absent response respectively of alpha-subunit release. Such a relationship was less evident with respect to the effects of SMS201-995, bromocriptine. TRH and GHRH on GH and PRL release. We conclude that basal and secretagogue-induced alpha-subunit release by cultured pituitary adenoma cells from acromegalic patients closely follows the pattern of GH release while such a relationship for GH and PRL is present only in a subgroup of the adenomas secreting GH and PRL simultaneously.

The characteristics and dynamics of hormone secretion in vivo and in vitro were investigated in six patients with gonadotropin-secreting pituitary adenomas. All six tumors secreted and contained FSH and different combinations of LH, beta-LH, and alpha-subunit. In addition, immunohistochemical examination of the pituitary tumor tissue showed staining with both LH and FSH in three and either LH or FSH in the other three tumors. TRH and GnRH stimulated hormone secretion in vivo and in vitro, and they also increased the hormone content of the cultured tumor cells. Bromocriptine significantly inhibited hormone release and reduced the hormone content of the tumor cells. In vivo, 2.5 mg bromocriptine significantly suppressed plasma hormone levels; the inhibiting effect on alpha-subunit concentrations was in general more marked than that on LH and FSH. We conclude that hormone release by gonadotropin-secreting pituitary adenomas can be stimulated by TRH and GnRH and inhibited by bromocriptine. Most of these tumors synthesize FSH, but there is a wide variation in the production of LH, beta-LH, and alpha-subunits. The sensitivity of hormone release to bromocriptine suggests that chronic therapy with this drug might have a beneficial effect on pituitary tumor size.