Histidyl-proline diketopiperazine suppresses prolactin secretion in human pituitary tumour cell cultures.

Because histidyl-proline diketopiperazine (HPD), a metabolite of TRH, has been shown to suppress prolactin (PRL) release by rat pituitary tumour cells, human pituitary tumour cells were exposed to this compound. Monolayer cell cultures were initiated from pituitary tissue removed by transsphenoidal surgery from two patients with prolactin-secreting microadenomas. Tumour fragments were mechanically dispersed; cells were seeded into multiwell plates and incubated in Ham's F-10 medium enriched with fetal calf serum (20%). HPD (7.5 ng/ml) suppressed PRL release by both tumour cell cultures. Theophylline reversed the inhibition of PRL release induced by HPD. The data raise the possibility that HPD may act as an endogenous prolactin-inhibiting factor in man.