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Biomedical subjects

J Kraicer

Publications and source records attributed to J Kraicer.

At least 19 recordsLinked to original sources
PubMed1995

Cytosolic protein kinase A mediates the growth hormone (GH)-releasing action of GH-releasing factor in purified rat somatotrophs.

The growth hormone (GH)-releasing action of GH-releasing factor (GRF) is known to be cAMP-dependent. However, definitive proof for the involvement of the cAMP-dependent enzyme protein kinase A (PKA) is still lacking. In this study, we characterized the PKA system in purified rat somatotrophs and examined its role in mediating GRF-stimulated GH release under static incubation conditions. PKA enzyme activity was detected only in the cytosolic, but not the particulate fraction of rat somatotrophs. This cytosolic PKA activity exhibited the characteristic cAMP dependence (with ED50 of 0.1 microM), ability to phosphorylate kemptide (a synthetic peptide with a PKA phosphorylation site), and susceptibility to inhibition by the bovine heat-stable PKA inhibitor. GRF treatment (1 pM-1 nM) stimulated the cytosolic PKA activity and GH release from rat somatotrophs in a dose-dependent manner. Time-course studies also demonstrated that activation of cAMP synthesis and PKA activity preceded the GH response to GRF. Stimulation of cytosolic PKA activity in rat somatotrophs by the adenylate cyclase activator forskolin (10 nM-1 microM) and membrane permeant cAMP analog db.cAMP (5 microM-0.5 mM) mimicked the GH-releasing effect of GRF. In contrast, Rp.cAMP, a cAMP antagonist for PKA regulatory subunits, blocked both the cytosolic PKA activity as well as GRF-induced GH release. Similar inhibitions were also observed when an inhibitor for PKA catalytic subunits, H89, was used. Somatostatin (SRIF) (1 nM), the physiological GH-release inhibitor, suppressed the GH response to GRF without affecting the basal or GRF-stimulated PKA activity. SRIF at a higher dose (10 nM) abolished the GH-releasing effect of GRF. In this case, SRIF also induced a small but significant inhibition of GRF-stimulated PKA activity. Taken together, the present study provides direct evidence that PKA enzyme activity is localized only in the cytosol of rat somatotrophs and constitutes an essential component of the signal transduction mechanism for GRF-stimulated GH release. This cytosolic PKA system, however, does not appear to be a major target for the GH-release inhibiting action of SRIF.

Animals↗
PubMed1995

Expression of mRNA for somatostatin receptor (sstr) types 2 and 5 in individual rat pituitary cells. A double labeling in situ hybridization analysis.

To characterize cell specific expression of sstr subtypes in the pituitary we have analyzed mRNA for sstr1-5 in rat pituitary somatotrophs by reverse transcriptase polymerase chain reaction and determined the pattern and level of expression of mRNA for sstr subtypes 2 and 5 in individual pituitary cell subpopulations by double label in situ hybridization. Purified somatotrophs expressed mRNA for all 5 sstrs. In situ hybridization analysis revealed sstr5 mRNA in 70% of somatotrophs, 57% of thyrotrophs, 38% of corticotrophs, 33% of lactotrophs, and 21% of gonadotrophs. mRNA for sstr2 occurred in 40% of somatotrophs, 36% of thyrotrophs, 26% of lactotrophs, 3% of corticotrophs, and 8% of gonadotrophs. Not only were more cells positive for sstr5 mRNA but the average number of autoradiographic grains/cell was also higher for sstr5 than sstr2. These results show expression of multiple sstr genes in individual pituitary cells. mRNA for sstr2 and 5 occur in each of the 5 major pituitary cell subsets, sstr5 mRNA being more widely and more abundantly expressed than sstr2.

Animals↗
PubMed1991

Growth hormone-releasing factor does not activate protein kinase C in somatotrophs.

The purpose of this study was to investigate the involvement of protein kinase C in growth hormone-releasing factor (GRF) action by directly measuring the effect of GRF on protein kinase C activity in purified male rat somatotrophs. Somatotrophs were incubated with GRF (10(-7) M) for 0.33, 1, 3, 10, 30 and 90 min. Protein kinase C present in soluble and particulate fractions was partially purified using DEAE-cellulose chromatography, and protein kinase C activity was assayed. In control experiments, to insure protein kinase C activity could be activated, two known protein kinase C activators, phorbol 12-myristate 13-acetate (PMA) and dioctanoyl-rac-glycerol (diC8) were added for 3 min. Protein kinase C activity is present in somatotrophs. Under basal conditions the majority of the enzyme activity is located in the cytosol (approximately 90%). The protein kinase C activators caused a significant translocation of protein kinase C activity from soluble to particulate fractions at 3 min. GRF did not cause a translocation of protein kinase C activity even though GH release was significantly increased by 3 min. GRF did not significantly alter the specific activity of protein kinase C in the soluble or particulate fractions, except for a small (approximately 10%) increase in soluble activity at 90 min. We conclude that protein kinase C is present in the somatotrophs of the anterior pituitary. Protein kinase C, however, does not mediate the action of GRF and its role in signal transduction in somatotrophs awaits elucidation.

Amino Acid Sequence↗
PubMed1991

Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs.

1. Somatotrophs from enzymatically dispersed anterior pituitary glands of rats, enriched to greater than 94% purity by density gradient centrifugation, were studied within 16 h of isolation using patch clamp recording methods in the conventional whole-cell and the perforated-patch configurations. 2. Rhythmic oscillations of membrane potential gave rise to action potentials in thirty-six of fifty-two cells studied with the perforated-patch technique. Membrane potential oscillated between approximately -70 mV and approximately -25 mV with an average frequency (mean +/- S.D.) of 0.9 +/- 0.9 s-1. 3. The current-voltage (I-V) relationship of cells was linear at negative potentials with outward rectification at potentials positive to -40 mV. Evidence that the outward current was due to K+ channels came from the deactivation tail currents, which reversed direction close to the K+ equilibrium potential (EK). The reversal potential shifted 60 mV per tenfold change of external K+ concentration ([K+]o), as expected for K+ current. 4. Suppression of outward current by tetraethylammonium (TEA) provided additional evidence for K+ current. Cd2+ reduced outward current, suggesting the presence of Ca(2+)-activated K+ conductance. 5. Depolarizing commands elicited transient inward Na+ current and a sustained Ca2+ current (ICa). ICa was recorded in isolation with Cs+ and TEA in the recording pipette and 10 mM-Ba2+ as the charge carrier. Activation of ICa began at approximately -40 mV, with peak inward current at 0 to +10 mV. The half-inactivation potential was approximately -35 mV. In addition, ICa was blocked by nifedipine. These characteristics indicate the presence of L-type Ca2+ channels in somatotrophs. 6. Somatostatin caused hyperpolarization and suppressed the spontaneous bursts of action potentials. Under voltage clamp, somatostatin activated an inwardly rectifying current that reversed direction near EK. When EK was altered by elevation of [K+]o, the reversal potential of the somatostatin-induced current shifted 55 mV per tenfold change of [K+]o, as predicted for a K+ current by the Nernst relation. The somatostatin-induced conductance (gK) was greater at more negative potentials, and the activation range shifted positive with elevation of [K+]o. 7. We conclude that freshly isolated rat somatotrophs possess Na+, Ca2+ and K+ currents. A large proportion of the cells exhibit spontaneous bursts of action potentials. Somatostatin activates an inwardly rectifying K+ conductance, causing hyperpolarization and cessation of spontaneous action potential activity, actions that would contribute to suppression of growth hormone release.

Action Potentials↗
PubMed1991

A comparison of the biological activities of authentic rat GRF(1-43)OH with the analogue rat GRF(1-29)NH2.

The purpose of this study was to characterize the biological activity of the synthetic rat growth hormone releasing factor analogue rGRF(1-29)NH2 and to compare its action on growth hormone (GH) release to that of authentic rGRF(1-43)OH. We first compared the concentration-response characteristics of the two peptides in static incubation, and then examined the reversibility and repeatability of the GH response in a perifusion system. Authentic rGRF(1-43)OH was significantly more potent in static incubation (EC50 = 3 x 10(-11) M) than the analogue (5 x 10(-11) M), whereas the reverse held true in perifusion. The shapes of the GH responses were similar for both peptides in the perifusion system. However, while the GH response to authentic rGRF was repeatable, the prior administration of rGRF(1-29)NH2 significantly reduced (greater than 50%) the GH response to the subsequent administration of either rGRF(1-29)NH2 or rGRF(1-43)OH. Thus authentic rGRF and the synthetic fragment may have different actions at the level of the GRF receptor or at a postreceptor (second messenger) step.

Animals↗
PubMed1991

Free intracellular Ca2+ concentration ([Ca2+]i) and growth hormone release from purified rat somatotrophs. I. GH-releasing factor-induced Ca2+ influx raises [Ca2+]i.

This study was carried out to investigate the role of free intracellular Ca2+ ([Ca2+]i) in the action of GH-releasing factor (GRF) by determining whether GRF causes and increase in [Ca2+]i and whether this increase results from changes in Ca2+ influx/efflux and/or mobilization of intracellular Ca2+ stores. We used a purified preparation of normal rat somatotrophs and examined the changes in 45Ca uptake, [Ca2+]i measured with indo-1, intracellular cAMP, and GH release induced by GRF. GRF stimulated a concentration-related biphasic increase in [Ca2+]i. Both the GRF-dependent increase in [Ca2+]i and GH release were blocked by incubation in low Ca2+ medium and by the organic Ca2+ antagonists nifedipine and diltiazem. The measurement of 45Ca uptake, in both steady state and nonsteady state conditions, demonstrated directly that GRF stimulates Ca2+ influx into somatotrophs. These data demonstrate that the GRF-stimulated increase in [Ca2+]i is dependent on Ca2+ influx. Redistribution of intracellularly stored Ca2+ could not be detected, even though intracellular Ca2+ stores were present. Therefore, the increase is due to Ca2+ influx, and the biphasic nature of the increase in [Ca2+]i induced by GRF is due to a difference in the rate of activation of Ca2+ influx and Ca2+ removal from the cytosol.

Animals↗
PubMed1991

Free intracellular Ca2+ concentration ([Ca2+]i) and growth hormone release from purified rat somatotrophs. II. Somatostatin lowers [Ca2+]i by inhibiting Ca2+ influx.

This study was carried out to investigate the role of Ca2+ in the somatostatin (SRIF)-induced inhibition of GH release. We examined the effect of SRIF on basal and GH-releasing factor (GRF)-induced increases in Ca2+ influx and free intracellular Ca2+ concentration ([Ca2+]i) in normal somatotrophs and examined the effect of SRIF on 45Ca uptake, [Ca2+]i measured with indo-1, and GH release. SRIF inhibited basal and GRF-induced GH release concurrently with a reduction in steady state 45Ca uptake. In nonsteady state experiments, SRIF also decreased basal 45Ca uptake. SRIF decreased baseline [Ca2+]i in a concentration-dependent manner and inhibited the GRF-induced biphasic increase in [Ca2+]i, but in a differential fashion. Low concentrations of SRIF abolished the peak (first phase) without affecting the plateau (second phase), while at high concentrations, both phases were inhibited. SRIF blocked the GRF-induced increase in [Ca2+]i regardless of whether it was applied before or during GRF stimulation. These data indicate that the SRIF-dependent decrease in 45Ca uptake is due to a decrease in Ca2+ influx. This is further supported by the fact that the GRF-dependent increase in [Ca2+]i, which is dependent on Ca2+ influx, is blocked by SRIF. The reported ability of SRIF to reduce the activation rate of Ca2+ currents, decrease Ca2+ conductance, and hyperpolarize the cell would explain the differential effect of SRIF on the GRF-induced [Ca2+]i increase. The inhibitory effect of SRIF on GH release would then be dependent on the ability of SRIF to decrease, or prevent, an increase in [Ca2+]i.

Animals↗
PubMed1991

Free intracellular Ca2+ concentration and growth hormone (GH) release from purified rat somatotrophs. III. Mechanism of action of GH-releasing factor and somatostatin.

GH-releasing factor (GRF)-stimulated GH release is dependent on a biphasic increase in free intracellular Ca2+ concentration [( Ca2+]i), resulting from an influx of Ca2+ into somatotrophs, while the inhibitory action of somatostatin (SRIF) on basal and GRF-induced GH release results from its ability to lower [Ca2+]i by inhibiting Ca2+ influx. This study was carried out to investigate the mechanism by which GRF and SRIF regulate [Ca2+]i to control GH release. The roles of ion channels, cAMP-dependent processes, and protein kinase-C (PKC) were investigated by measuring changes in [Ca2+]i, 45Ca influx, and GH release when purified rat somatotrophs were exposed to high K+, cAMP analogs, prostaglandin E2, as well as the PKC activators 1,2-dioctanoyl-glycerol and phorbol 12-myristate 13-acetate. High K+ depolarization produced a rapid and transient increase in [Ca2+]i, while cAMP and prostaglandin E2 led to a sustained elevated [Ca2+]i. PKC activators produced a transient increase in [Ca2+]i, followed by a decrease to below baseline. All secretagogues tested raised [Ca2+]i by stimulating Ca2+ influx through L-type voltage-sensitive Ca2+ channels (VSCC), since the increases in [Ca2+]i were blocked by incubation in Ca2(+)-free medium and by the dihydropyridine Ca2+ antagonist nifedipine. SRIF lowered [Ca2+]i by blocking the Ca2+ influx stimulated by all of these GH secretagogues except high K+. These results are consistent with the model in which GRF initiates its action by increasing Na+ conductance to depolarize the somatotroph via cAMP. This depolarization would stimulate Ca2+ influx through VSCC, which would result in the first phase of the GRF-dependent increase in [Ca2+]i. This increase in [Ca2+]i would stimulate Ca2+ removal from the cytosol by activating Ca-ATPase via Ca-calmodulin and/or PKC. This would result in the lowering of [Ca2+]i to the plateau level of the second phase of the GRF response. SRIF prevents the GRF-induced increase in [Ca2+]i by increasing K+ conductance and, thus, hyperpolarizing the cell. Hyperpolarization would close VSCC, leading to a decrease in Ca2+ influx, with a subsequent drop in [Ca2+]i.

Animals↗
PubMed1990

Effect of growth hormone-releasing factor on phosphoinositide hydrolysis in somatotrophs.

We studied the role of the phosphatidylinositol system in the action of growth hormone-releasing factor (GRF). We asked whether GRF stimulates the activity of phospholipase C by determining GRF-induced changes in 32P labeling of the individual phosphoinositides and inositol phosphates in purified rat somatotrophs. The somatotrophs were challenged with GRF (10(-7)M) for 0.33, 1, 3, 10, 30, and 90 min. GRF did not significantly or consistently alter 32P incorporation into phosphatidylinositol bisphosphate (PIP2), phosphatidylinositol monophosphate (PIP), or phosphatidylinositol (PI), except for a small reduction in PIP labeling at 90 min. In general the level of 32P incorporation into the inositol phosphates did not increase but instead decreased with GRF. There was a small but significant reduction of labeling of inositol trisphosphate (IP3) at 90 min of GRF incubation. There were also small but significant decreases in 32P incorporation into inositol bisphosphate (IP2) at 0.33, 3, and 30 min. GRF did not significantly alter 32P labeling of inositol monophosphate (IP). These results indicate that GRF does not stimulate phospholipase C activity in somatotrophs. We conclude that the phosphatidylinositol second messenger system does not play an essential role in the action of GRF.

Animals↗
PubMed1989

Growth hormone-releasing factor-sensitive adenylate cyclase system of purified somatotrophs: effects of guanine nucleotides, somatostatin, calcium, and magnesium.

The purpose of this study was to characterize the adenylate cyclase system in a purified population of normal somatotrophs derived from rat pituitary and to determine the responses of this system to GRF, somatostatin, guanine nucleotides, and cations. Additionally, experiments were performed to evaluate the interrelationships among changes in adenylate cyclase activity, cellular cAMP levels, and GH release induced by GRF and somatostatin. The results obtained using homogenates and membrane preparations from somatotrophs included the following. 1) GRF caused guanine nucleotide-dependent concentration-related (Ka, approximately 10(-8) M) stimulation of adenylate cyclase activity. 2) Guanine nucleotides were effective in stimulating cyclase in the absence of GRF; the concentration of guanine nucleotide required for half-maximal stimulation was decreased more than 10-fold in the presence of GRF. 3) Adenylate cyclase activity increased with increasing concentrations of free Mg2+ (0.25-20 mM); activation by GRF and guanine nucleotide resulted in an approximately 7-fold increase in the enzyme's affinity for free Mg2+. 4) Somatostatin, up to 10(-6) M, did not alter basal or GRF-stimulated adenylate cyclase activity. 5) Ca2+ (0.5-11.9 microM) produced concentration-dependent inhibition of basal (up to 28%) and GRF-stimulated (up to 47%) cyclase activities; the inhibitory effect of Ca2+ was accompanied by a decrement (2- to 3-fold) in the apparent affinities of the enzyme for both GRF and guanine nucleotide. In intact somatotrophs, GRF produced concentration-dependent stimulation of GH release (Ka, approximately 6 x 10(-11) M), preceded by a marked elevation of cAMP levels. While somatostatin blocked GRF-induced GH release, the augmented cAMP levels were only slightly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1989

Protein kinase C is not essential for growth hormone (GH)-releasing factor-induced GH release from rat somatotrophs.

To examine the role of protein kinase-C in the mediation of GH release we used acutely dispersed purified somatotrophs in static incubation and acutely dispersed adenohypophyses in perifusion. In static incubation, activation of protein kinase-C by phorbol 12-myristate 13-acetate (PMA) and 1,2-dioctanoyl-rac-glycerol (diC8) resulted in an increase in GH release and a concurrent concentration-dependent increase in cAMP accumulation. The GH response to diC8 in perifusion was reversible and repeatable. On the other hand, the GH response to PMA was not repeatable. The lack of repeatability is most likely due to the depletion of protein kinase-C by prolonged treatment with PMA. This assumption is strengthened by the observation that 1 h of perifusion with PMA left the somatotrophs refractory to a subsequent application of diC8. When graded pulses of GRF were applied during treatment with PMA, the GH response to GRF was not altered. Somatostatin reduced (in static incubation) or blocked (in perifusion) the release of GH induced by diC8 and PMA, but the accumulation of cAMP was not affected. We conclude that 1) activation of protein kinase-C in normal somatotrophs results in GH release which may not be completely independent of the cAMP pathway; 2) activation of protein kinase-C is not essential for GRF-induced GH release; and 3) SRIF acts at a site distal to or independent of cAMP to inhibit GH release induced by activators of protein kinase-C.

Animals↗
PubMed1988

Neuropeptide Y does not inhibit the release of alpha-MSH from the pars intermedia of the rat adenohypophysis.

Neuropeptide Y in concentrations from 10(-8) to 10(-6) M inhibits the release of alpha-MSH from the frog (Rana pipiens) pituitary in a reversible, sustained, and concentration-related manner. However, it does not inhibit the release of alpha-MSH from the rat pars intermedia. Thus, while neuropeptide Y may play a role in the control of alpha-MSH release in amphibia, it appears not to be a regulatory peptide for the mammalian pars intermedia.

Animals↗
PubMed1988

Release of growth hormone from purified somatotrophs: effects of the calcium channel antagonists diltiazem and nifedipine on release induced by growth hormone-releasing factor.

We examined the effect of the voltage-sensitive Ca2+ channel antagonists, diltiazem and nifedipine, on basal and stimulated growth hormone (GH) release from purified somatotrophs. Our aim was to ascertain whether an influx of Ca2+ from the extracellular to the intracellular compartment is essential for augmented release. Basal release was decreased in a concentration-dependent manner by both diltiazem and nifedipine, while cAMP accumulation was unaffected. The release of GH induced by 29 mM K+ was blocked by diltiazem and nifedipine, at 10(-7) and 10(-8) M, respectively. Again cAMP was unaffected. The release of GH induced by growth hormone-releasing factor was significantly reduced by 10(-4) M diltiazem and completely blocked by nifedipine at a concentration of 10(-6) M or greater. Where the antagonists were effective, the growth hormone-releasing factor induced increase in cAMP accumulation was augmented. We conclude that an influx of Ca2+ from the extracellular compartment is essential for stimulated GH release.

Animals↗
PubMed1988

Failure of growth hormone (GH) to feed back at the level of the pituitary to alter the response of the somatotrophs to GH-releasing factor.

GH feeds back at the level of the central nervous system to alter the release of somatostatin and GRF, resulting in altered GH release. The purpose of this study was to see whether the concentration of GH, impinging directly on the somatotrophs of the adenohypophysis, would alter the responsiveness of the somatotrophs to GRF. Using a perifusion system and dispersed pituitary cells, we found that the GH response to a pulse of GRF is unaltered over a wide range of GH concentrations. We conclude that GH does not feed back at the level of the adenohypophysis to alter the responsiveness of the somatotrophs to GRF.

Animals↗
PubMed1988

Effect of withdrawal of somatostatin and growth hormone (GH)-releasing factor on GH release in vitro.

The secretion of GH, in vivo, is pulsatile. We have proposed that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, while the magnitude of the bursts is set by the amount of GH-releasing factor (GRF) impinging on the somatotrophs, before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to further examine the interaction between GRF and SRIF on the magnitude of the burst of GH release that follows SRIF withdrawal. We first characterized the GH response, with time, to constant perifusion with GRF. The initial burst, followed by a rapid decrease in GH release induced by constant perifusion is due to a loss of GRF bioactivity in the perifusion medium and not to a decreasing responsiveness of the somatotrophs. This was followed by studies on the interaction between GRF and SRIF. The burst of GH release after cessation of perifusion with SRIF (10(-9) M) plus GRF (10(-10) M) can be blocked by the administration of SRIF during the burst. Also, the magnitude of the burst is proportional to the concentration of GRF preceding the withdrawal of SRIF. It is likely that similar relations apply in vivo, where SRIF withdrawal sets the timing and duration of the episodic burst of GH release, while GRF sets the magnitude.

Animals↗
PubMed1986

Effect of somatostatin withdrawal and growth hormone (GH)-releasing factor on GH release in vitro: amount available for release after disinhibition.

The secretion of GH is strikingly episodic. We have suggested that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, whereas the magnitude of the bursts is determined by the amount of GH-releasing factor (GRF) impinging on the somatotrophs before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to examine the interaction of SRIF and GRF on GH release and, in particular, to examine the effect of GRF on the magnitude of the burst of GH release that follows SRIF withdrawal. After 30 min of perifusion with SRIF (10(-9) M), there follows an immediate but small burst of GH release. The burst of GH release following concurrent perifusion with SRIF plus GRF (10(-10) M) is increased, with a 7.5- to 9.5-fold increase in the peak secretion rate. When GRF is maintained after the withdrawal of SRIF, the peak secretion rate is not different from that seen after simple withdrawal of both SRIF and GRF, but the duration of the burst is increased. These data demonstrate that the presence of GRF during SRIF perifusion, while not altering basal release, does strikingly increase the post-SRIF release of GH. We propose that a similar relation applies in vivo, where SRIF withdrawal sets the timing of the episodic bursts of GH release, whereas GRF determines the magnitude.

Animals↗
PubMed1985

Release of pro-opiomelanocortin-derived peptides from the pars intermedia and pars distalis of the rat pituitary: effect of corticotrophin-releasing factor and somatostatin.

The parenchymal cells of the pars intermedia (PI) and corticotrophs of the pars distalis (PD) synthesize pro-opiomelanocortin (POMC), which, through posttranslational processing, gives rise to a group of structurally related peptides, including MSHs, ACTH, CLIP, LPHs and endorphins. We investigated the control of release of these peptides using an in vitro system. We perifused either intact neurointermediate lobes (NI) or PD halves obtained from rats. Perifusion medium and tissue extracts were subjected to a battery of bioassays (BA) and radioimmunoassays (RIA) (including MSH-BA, alpha-MSH-RIA, ACTH-BA, ACTH-RIA, LPH-RIA) and a receptor-binding assay for morphine-like activity (MLA). The relative amounts of released peptide activities were examined under basal conditions and after challenging with synthetic ovine corticotrophin-releasing factor (CRF) and somatostatin. CRF stimulated the release of all assayed peptides from both the PD and PI in a dose-related manner. Stimulated release was immediate (within 3 min), constant, reversible and repeatable. Somatostatin (up to 100 ng/ml) did not alter basal release from either PD or PI. Somatostatin did block CRF-induced release from the PI but not from the PD. These observations support an action of both CRF and somatostatin in the control of secretion of POMC-derived peptides from the PI.

Adrenocorticotropic Hormone↗