Differential Spontaneous and Stimulated in vitro Release of Newly Synthesized or Stored rGH and rPRL by Pituitaries from Rats with Hypothalamic Lesions

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Abstract
These experiments were designed to examine which aspects of basal and responsive somatotroph and lactotroph synthesis and release behavior in vitro are functions of in vivo tonic hypothalamic environment. Although we cannot specifically define in vivo hypothalamic tone, we show that spontaneous rates of hormone synthesis and release in vitro, as well as release in response to a secretagogue, are influenced by altered in vivo hypothalamic tone. This work combines in vivo destruction of hypothalamic (ventromedial [VMN] or dorsomedial [DMN]) nuclei with in vitro double-label perifusion to track hormone synthesis and release of newly synthesized and stored hormone. We demonstrate that hormone synthesis rates are greater in DMN-lesioned (DMNL) or sham-operated (SHAM) animals than in VMN-lesioned (VMNL) animals and that DMNL and SHAM synthesis rates fall with time outside the hypothalamic environment. We show that basal release of newly synthesized rGH by DMNL tissue exceeds that of SHAM, while release from VMNL tissue is less than that of SHAM. Accidental placement of small bilateral lesions between and not impinging on either the DMN or VMN nuclei did not alter newly synthesized rGH release but accelerated newly synthesized rPRL release. Although basal fractional release of stored growth hormone and prolactin was the same for the three groups, potassium ion-induced release of stored hormone was similar in DMNL or SHAM tissue, but depressed in VMNL tissue. Thus, the creation of definable hypothalamic damage in a living animal produced specific modifications in in vitro pituitary synthetic/secretory behavior, presumably by reproducibly altering hypothalamic secretion. Within the limits of the lesion technique and defined experimental options, somatotroph and lactotroph synthetic/secretory behavior predicted the hypothalamic lesion. We conclude that resting rGH and rPRL synthesis, release, as well as storage compartmentalization in vitro exhibit specific and independent variability indicative of the in vivo hypothalamic environment from which the tissue was obtained.