Release of pituitary growth hormone by prostaglandins and dibutyryl adenosine cyclic 3':5'-monophosphate in the absence of protein synthesis.
01 Nov 1970-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 67, Iss: 3, pp 1172-1179
TL;DR: Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone, and although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone.
Abstract: Effects of prostaglandins on the incorporation of [4,5-3H]leucine into growth hormone and its subsequent release into the incubation medium were studied. Incubation of rat anterior pituitary glands with 10-6 M prostaglandin PGE1 in tissue culture medium 199 for 7 hr caused a 40-300% increase in the release of labeled growth hormone into the incubation medium. PGE1 at 10-8 M increased growth hormone synthesis but not release. At 10-6 M, PGE2 had effects similar to PGE1; PGA1 increased growth hormone synthesis but not release. PGF2α was without effect on either synthesis or release of growth hormone.
Prolactin synthesis and release were not affected by prostaglandins. All of the prostaglandins, at 10-4 M, increased adenyl cyclase activity in the pituitary gland but phosphodiesterase activity was unaltered. Dibutyryl cyclic AMP, with or without caffeine, caused an up to 300% increase in labeled growth hormone release. No consistent effect of prolactin was observed. If potassium concentration was increased 10-fold, a 215% increase in growth hormone release was observed. A combination of hypertonic potassium and 10-6 M PGE1 increased growth hormone release 325%, suggesting that potassium and prostaglandins act by independent mechanisms. Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone. Although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone. Similarly, puromycin inhibited synthesis of growth hormone but did not block release induced by prostaglandin, dibutyryl cyclic AMP, theophylline, or fluoride. Prostaglandins increase pituitary adenyl cyclase activity and, presumably via cyclic AMP, increase growth hormone release, independently of protein synthesis.
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TL;DR: The hypothesis that prostaglandins play a functional role in regulating the release of LH necessary for ovulation in the rat is supported.
306 citations
TL;DR: The results demonstrate that function and morphologic integrity are preserved in this cell system, suitable for the study of various aspects of pituitary secretion and its control.
Abstract: A new procedure has been developed for dissociating anterior pituitary tissue and producing a viable suspension of single cells. The procedure involves incubation of small tissue blocks in 1 mg/ml trypsin (15 min), followed by incubation in 8 µg/ml neuraminidase and 1 mM EDTA (15 min), followed by mechanical dispersion. Cell yields are ∼55%, based on recovered DNA. By electron microscopy five types of secretory cells (somatotrophs, mammotrophs, thyrotrophs, gonadotrophs, and corticotrophs) plus endothelial and follicular cells can be identified and are morphologically well preserved up to 20 h after dissociation. Throughout this period, the cells incorporate linearly [3H]leucine into protein for up to 4 h at a rate 90% greater than hemipituitaries, and they synthesize, transport intracellularly, and release the two major pituitary secretory products, growth hormone and prolactin. Immediately after dissociation the cells' ability to respond to secretogogues (high K+ and dibutyryl cyclic AMP) is impaired, but after a 6–12-h culture period, the cells apparently recover and discharge 24% and 52%, respectively, of their content of prelabeled growth hormone over a 3-h period in response to these two secretogogues. This represents a stimulation of 109% and 470% over that released by cells incubated in control medium. The results demonstrate that function and morphologic integrity are preserved in this cell system. Therefore it is suitable for the study of various aspects of pituitary secretion and its control.
236 citations
TL;DR: It is speculated that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.
139 citations
137 citations
TL;DR: Prostaglandin functions are reviewed including the role of PGs in the hypothalamic and pituitary control of gonadotropin secretions; and their roles in ovulation, 3) in luteinization, and 4) in corpus luteum regression.
Abstract: PIP: Some aspects of prostaglandin (PG) functions are reviewed including: 1) the role of PGs in the hypothalamic and pituitary control of gonadotropin secretions; and 2) their roles in ovulation, 3) in luteinization, and 4) in corpus luteum regression. PGE1 is known for its role in stimulation of increased cyclic adenosine 3',5' monophosphate (cAMP) and hormone secretion in the anterior pituitary. Direct effects of PGs on the secretion of luteinizing hormone, follicle stimulating hormone, and adrenal cortex hormones are not clearly known, but surmised. Such actions may not be the direct effects of PGs on pituitary action. Instead, more studies on receptor functions for PGs in pituitary cells are needed. Systemic administration of PGs has been shown to increase circulating levels of gonadotropins, adrenal cortex hormones, prolactin, follicle stimulating hormone, and luteinizing hormone; and in general, PGs of the E series are more potent than those of the F series. This response to systemic administration seems to be caused by an hypothalamic site of action, a conclusion based on several observations, including the observation that direct application of PGs to brain tissue causes a mimicking of endogenous PG effects of gonadotropin secretion. PGs also play a role in ovulation. Elevated PG levels in follicular tissues are induced by gonadotropins; cyclic nucleotides may be involved in mediating the action of gonadotropins on follicular PG production; a recognized time lag after exposure of the follicle to gonadotropin or cyclic nucleotides indicates that macromolecular synthesis may be involved in follicular PG production; and plasminogen activator may play a role in the process of follicular rupture that leads ot ovulation. The role of PGs in luteinization has been suggested by experiments which showed that granulosa cells cultured with PGE1 and PGE2 luteinized. PGs, particularly PGF2 alpha, cause luteal regression in many species, except perhaps in humans. And PGF2 alpha may be an antagonist of gonadotropin action in the corpus luteum. A proposed mechanism of PGF2 alpha-induced luteolysis in rats is also presented.
122 citations