Growth Hormone-Releasing Factor-44 Specificity for Components of Somatotroph and Lactotroph Immediate Release Pool Substructures*

Abstract

Rat somatotroph and lactotroph hormone storage is divisible into at least two functional compartments: an immediate release pool (IRP) and a pool that responds to prolonged stimulation. An IRP substructure has been defined by release in response to potassium ion (K+), prostaglandin E1 (PGE1), and Bu2cAMP. The somatotroph IRP is expandable; the lactotroph IRP is fixed in size. The present experiments examined which IRP components contribute to the rapid release of stored GH in response to GH-releasing factor-44 (GRF). Release of stored PRL was monitored for comparison. In vitro prelabeling defined stored rat (r) GH and rPRL. Release in response to 21 mM K+, 3 microM PGE1, 1 mM Bu2cAMP, and/or 3 nM GRF was monitored with a perifusion-immunoprecipitation system. After 120 min of basal perifusion, tissue was exposed to one of the four secretagogues for 90 min. During a second 90-min period a second secretagogue was added while exposure to the first secretagogue continued. We demonstrated that 21 mM K+ reduces peak rGH release in response to 3 nM GRF by 52%, whereas GRF does not reduce rGH release in response to K+; 3 microM PGE1 reduces rGH release in response to GRF by only 19% although GRF reduces rGH release in response to PGE1 by 88%; 1 mM Bu2cAMP reduces rGH release in response to GRF by 87%, and GRF eliminates rGH release in response to Bu2cAMP (1.2% of control value); combined K+ plus Bu2cAMP reduce rGH release in response to GRF to 2.5% of the control value, whereas after GRF pretreatment rGH release in response to combined K+ plus Bu2cAMP is 93% of the control value; and combined PGE1 and Bu2cAMP reduce the response to GRF to 17% of the control value. Effects on rPRL release are qualitatively similar. We conclude that immediate GRF-stimulated release of stored rGH originates in the somatotroph IRP components defined by responses to PGE1 and Bu2cAMP; it derives only slightly, if at all, from the IRP component defined by the response to K+. The smaller GRF-stimulated release of IRP rPRL is similarly derived.

Joint pituitary-hypothalamic and intrahypothalamic autofeedback construct of pulsatile growth hormone secretion

“…Moreover, the replenishable GH pool model is obligatory to simulate post-SRIF rebound release of GH in the female formulation, wherein GH autofeedback is attenuated. Both projected outcomes agree with experimental data in the adult rat (37,42,45,46). And, third, systemic exposure to SRIF inhibits GH secretion, which in the present construct limits endogenous SRIF restraint and (on SRIF withdrawal) induces rebound-like GH release.…”

“…Individual peptide elimination rates are assumed to be distinct and stable. The primary network-like connections (and their experimental derivation) are 1) GHRH's acute stimulation of GH release from somatotrope cells (8,18,26,30,37,42,43,45,46), 2) SRIF's antagonism of GHRHinduced GH secretion (18,20,34,42), 3) GH's delayed feedforward on SRIF release (6,9,29,31,34,35,37), 4) SRIF's inhibition of GHRH secretion (8,12,16,24,30), 5) GH's repression of GHRH outflow (7,9,16,31,32), 6) GHRH's time-lagged induction of pituitary SRIF secretion (1, 2, 11, 24, 27, 29, 32-34, 37, 46), and 7) GHRH's induction of the de novo synthesis and accumulation of (releasable) GH in the pituitary gland (20,34,42,45,46). This ensemble formulation extends an earlier basic construct by including intrahypothalamic GHRH-evoked SRIF outflow and GHRH-stimulated synthesis and accumulation of GH stores (see DISCUS-SION).…”

“…In vitro and in vivo SRIF blocks the release, but not GHRHstimulated synthesis and accumulation, of GH in somatotrope cells (18,20,35,45,46). Equations 1 and 4 incorporate this precept by allowing GHRH to promote the (saturable) accumulation of releasable GH stores when SRIF is present.…”

Fractional Reduction of Somatostatin Concentration Interacted with Rat Growth Hormone Releasing Hormone to Titrate the Magnitude of Pulsatile Growth Hormone and Prolactin Release in Perifusion

“…In those experim ents we also showed that sim ulta neous exposure to com bined SRIF and BuicAMP resulted in a rate of GPI release that was indistinguishable from the basal release rate [26]; in terms of net horm one release, these two secretagogues, therefore, cancelled each other's effects. We suggested a mechanism for the progressive seq uestration o f the intracellular horm one that is released after SRIF withdrawal [26,29,30] and supported the suggestion with an electron microscopic dem onstration of a juxtam embrane granule pool [27].…”

Immunocytochemical and Immunoelectron-Microscopic Study of Somatotrophs in ICR and Nonobese Diabetic Mice

“…Part of newly synthesized GH was immediately released, and most of the newly synthesized GH was stored as secretory granules in the cytoplasm [Stachura and Tyler, 1987]. It is not clear that this may be dependent upon either the existence of separate intracellular pathways for the release and storage of GH, or the presence of functionally specialized subsets of GH cells within heterogeneous GH cell population.…”