DIFFERENTIAL INNERVATION OF INDIVIDUAL MELANOTROPES SUGGESTS A ROLE FOR NONSYNAPTIC INHIBITORY REGULATION OF THE DEVELOPING AND ADULT-RAT PITUITARY INTERMEDIATE LOBE

Dopamine and GABA were detected in intermediate lobe axons around birt h, and early axons were closely apposed to glial cells and processes, possibly using them for guidance. In the adult, axons containing coloc alized dopamine and GABA were distributed in a distinct pattern within the lobe, with plexuses located dorsally and ventrally. Axons prefere ntially followed glial processes in interlobular septa, pet were also interspersed between melanotropes. Individual melanotropes were contac ted by varying numbers of axon terminals, with some devoid of contacts . Boutons contained both small clear vesicles and large dense-cored ve sicles; membrane specializations were not well-developed. From these f indings we concluded that in addition to direct synaptic inhibition, d opamine and GABA could stimulate their receptors by mechanisms similar to ''parasynaptic'' [Schmitt (1984) Neuroscience, 13:991-1001] or ''v olume'' [Agnati et al. (1995) Neuroscience, 69:711-726] transmission a s proposed for the CNS. Humoral agents passing into the intermediate l obe from portal vessels, thus acting as classical hormones, further re gulate the melanotropes. Moreover, approximately 50% of the axonal ele ments were closely apposed to glia, suggesting that glia could have re gulatory roles. Previous studies from our laboratory [Chronwall et al. (1987) Endocrinology, 120:1201-1211; Chronwall et al. (1988) Endocrin ology, 123:1992:1202] demonstrated heterogeneity in proopiomelanocorti n (POMC) biosynthesis among individual melanotropes, prompting the hyp othesis that the degree of innervation could govern the expression of certain molecules. We combined immunohistochemistry and in situ hybrid ization histochemistry to evaluate whether melanotrope molecular heter ogenity is spatially correlated with axons and terminals. Tentatively, melanotropes expressing low levels of POMC and ale subunit P/Q type C a2+ channel mRNAs often were apposed to axons, whereas those with low levels of D-2L receptor mRNA rarely were contacted by axons, suggestin g that innervation could be one of the factors inducing and maintainin g heterogeneity. (C) 1998 Wiley-Liss, Inc.