Project: Research project

Project Details


Recent clinical investigations of pituitary function suggest that pituitary
adenomata may result from pituitary stimulation by releasing factors of
hypothalamic or ectopic origin. Feedback on many secretory cells by their
own secretory products is knows to modulate their response. In preliminary
studies of a strain of rat pituitary tumor cells (GH3) which secrete both
prolactin (PRL) and growth hormone (H) we have observed: (1) specific
inhibition of hormone synthesis and secretion in tissue culture when medium
hormone nears 1 Mug/ml; (2) stable hormone synthesis and secretion in the
first 10-12 hours of perifusion; (3) a spontaneous increase in the rate of
PRL synthesis and secretion after 10-12 hours and a separate spontaneous
increase in the rate of GH synthesis and secretion at 20-28 hours of
perifusion of the same cells; (4) continuing increase in the rate of
hormone synthesis and release for 80 hours of perifusion; (5) complete and
specific inhibition of the spontaneous increase of PRL synthesis and
secretion by adding 600 ng/ml rPRL to perifusion medium; and (6) a
suggestion of similar specific inhibition of GH, but not PRL, by 600 ng/ml
of rGH. This application proposes (1) in the GH(3) tumor cell to: (a)
characterize maximum synthesis and secretory capacity for each hormone, (b)
define factors such as specific hormone receptors, and dependency upon DNA,
RNA, and/or protein synthesis, which influence the spontaneous increase in
hormone release, (c) investigate the specificity of the feedback response
using placental lactogen (PL); and (2) in the normal rat to: (a) pursue a
qualitatively similar phenomenon in intact pituitaries as well as in
somatotrophs and lactotrophs isolated by density gradient centrifugation
seeking quantitative differences in responsivity, and (b) compare synthesis
and release responses to hypothalami or hypothalamic extracts at various
ambient hormone levels. Proposed experiments are performed in tissue
culture, pituitary and cell perifusion, and in vivo. Radioimmunoassay
follows general hormone release and specific immunoprecipitation
differentially follows release of stored hormone and synthesis and release
of newly synthesized hormone. This work will enhance understanding of the
regulation of normal pituitary hormone control mechanisms, may contribute
to understanding the genesis of pituitary adenomate and will consider
possible physiologic interrelations between GH, PRL and PL.
Effective start/end date6/1/816/30/88


  • Medicine(all)