NERVE GROWTH-FACTOR IN THE ANTERIOR-PITUITARY - LOCALIZATION IN MAMMOTROPH CELLS AND COSECRETION WITH PROLACTIN BY A DOPAMINE-REGULATED MECHANISM

Nerve growth factor (NGF) is well characterized for its neurotrophic a ctions on peripheral sensory and sympathetic neurons and on central ch olinergic neurons of the basal forebrain. Recent evidence, however, ha s shown high levels of NGF to be present in a variety of biological fl uids after inflammatory and autoimmune responses, suggesting that NGF is a mediator of immune interactions. Increased NGF serum levels have been reported in both humans and experimental animal models of psychol ogical and physical stress, thus implicating NGF in neuroendocrine int eractions as well. The possible source(s) and the regulatory mechanism s involved in the control of serum NGF levels, however, still remain t o be elucidated. We now report the presence of both NGF gene transcrip ts and protein in the anterior pituitary. immunofluorescence analysis indicated that hypophysial NGF is selectively localized in mammotroph cells and stored in secretory granules. NGF is cosecreted with prolact in from mammotroph cells by a neurotransmitter-dependent mechanism tha t can be pharmacologically regulated. Activation of the dopamine D-2 r eceptor subtype, which physiologically controls prolactin release, res ulted in a complete inhibition of vasoactive intestinal peptide-stimul ated NGF secretion in vitro, whereas the specific D-2 antagonist (-)-s ulpiride stimulated NGF secretion in vivo, suggesting that the anterio r pituitary is a possible source of circulating NGF. Given the increas ed NGF serum levels in stressful conditions and the newly recognized i mmunoregulatory function of this protein, NGF, together with prolactin , may thus be envisaged as an immunological alerting signal under neur onal control.