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Biomedical subjects

A Enjalbert

Publications and source records attributed to A Enjalbert.

At least 91 records · Page 5Linked to original sources
PubMed1989

Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells.

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.

Angiotensin II↗
PubMed1989

Somatostatin receptors in brain and pituitary.

Somatostatin (SRIF) actions in the brain and pituitary are mediated by specific receptors. Using radioiodinated ligands it has been possible to characterize the kinetics of specific binding sites in the brain and pituitary, and to determine their cellular localization by autoradiography. At the pituitary level, the inhibition of growth hormone, prolactin and thyrotropin secretions induced by SRIF is mediated through a single binding site which is coupled to the inhibition of adenylate cyclase. In the brain, SRIF receptors are localized on neurons and glial cells and are also coupled to adenylate cyclase inhibition. Two sites are differentiated in the brain with an analogue of somatostatin, SMS 201995. In humans, SRIF-binding sites have been related to a number of pathologies. At the pituitary level, it has been shown that the number of binding sites was negatively correlated to growth hormone levels in acromegaly. Furthermore, SRIF-binding sites were undetectable in a patient which did not respond to SMS 201995 therapy. In the brain, meningiomas and gliomas are rich in SRIF binding sites. This suggests a possible role for SRIF on glia. In neurodegenerative diseases, cortical SRIF concentrations are decreased in Alzheimer's and Parkinson's disease associated with dementia while SRIF-binding sites are only affected in Alzheimer's disease. In conclusion, the physiological role of SRIF in the brain and pituitary can be evaluated by studying the receptors of the peptide. Such studies allow to question the implication of SRIF in endocrine and neuropathologies.

Animals↗
PubMed1989

Resistance to bromocriptine in prolactinomas.

Bromocriptine therapy normalizes PRL secretion in most, but not all, patients with prolactinomas. This study was undertaken to determine the mechanism(s) responsible for bromocriptine resistance in patients with a PRL-secreting macroadenomas (n = 5) or microadenomas (n = 3). Their mean basal plasma PRL value was 807 +/- 220 (+/- SE) micrograms/L before treatment, and their nadir mean value was 354 +/- 129 micrograms/L during chronic therapy with 15-30 mg bromocriptine daily; four of the eight patients had an increase in tumor size during therapy. In cultures of prolactinoma cells from patients normally responsive to bromocriptine therapy (n = 10), considered as controls, 10(-9) mol/L bromocriptine inhibited PRL release by 71 +/- 6% (+/- SE), and the half-inhibitory dose was 7 x 10(-11) mol/L. In contrast, in cultures of prolactinoma cells from five patients resistant to bromocriptine, PRL release was inhibited by only 3-42% at 10(-9) mol/L bromocriptine. This partial inhibition was reversed by a 100-fold excess of haloperidol. In contrast, the effects of other inhibitors of PRL release (10(-8) mol/L T3 and 10(-8) mol/L somatostatin) or of a stimulator (10(-8) mol/L angiotensin-II) on cells from resistant and normally responsive patients were similar. In cell membranes from five bromocriptine-responsive adenomas the density of dopaminergic binding sites, labeled by [3H] spiroperidol was 243 +/- 65 (+/- SE) fmol/mg protein. In adenomas from the eight patients resistant to bromocriptine therapy the density of [3H]spiroperidol-binding sites lower (145 +/- 31 fmol/mg protein). In adenomas from five resistant patients whose tumor had grown during therapy the density of binding sites was 25 +/- 3 fmol/mg protein, 10% of that in normally responsive patients. The effects of dopamine on adenylate cyclase activity also were different in the three groups of adenomas. Dopamine inhibited adenylate cyclase activity by 28.8 +/- 5.6% in five bromocriptine-responsive tumors and by 16.5 +/- 4.3% in adenomas from eight resistant patients. In contrast, in the five patients whose tumors grew during therapy dopamine paradoxically stimulated adenylate cyclase activity (+26.4 +/- 9.8%). There was a very good correlation between the density of dopaminergic binding sites and maximal inhibition of adenylate cyclase activity in bromocriptine-responsive prolactinoma patients (r = 0.90) and resistant patients who had no tumor growth during therapy (r = 0.94).(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxycorticosteroids↗
PubMed1989

Evidence for direct action of calcitonin in the rat pituitary gland.

Classic concepts of calcitonin (CT) function have focused on the effects of CT on calcium homeostasis. More recently CT actions on brain and pituitary have been investigated. In order to evaluate the effects of CT on the anterior pituitary gland we studied the action(s) of CT in vitro and visualized endogenous CT in adult male rat pituitary gland by immunocytochemistry on ultrathin sections obtained by cryoultramicomy. In vitro study using dispersed anterior pituitary cells indicated that CT stimulated the secretion of PRL, whereas the secretion of GH, TSH and LH was not affected. CT-like immunoreactivity was observed in lactotropes only. The other pituitary cell types were not immunoreactive. In lactotropes, immunostaining was observed in the cytoplasm and in the nucleus. In the cytoplasm, CT-like immunoreactivity was visuzalized in the cytoplasmic matrix and in the secretory granules. In the nucleus, immunostaining was distributed primarily in the euchromatin, in the vincinity of heterochromatin region. CT-like immunoreactivity was also observed at the plasma membrane but was only scarce. No reaction product was found when anti-CT serum pre-incubated with CT was used. In conclusion, these results bring evidence for a direct action of CT on lactotrope regulation in vitro as well as in intact animals.

Animals↗
PubMed1988

Displaceable somatostatin binding sites in the gray matter and pyramidal paths of the human developing spinal cord.

The binding of the somatostatin analogue, 125I-iodo-Tyr-[Tyr0,D-Trp8]S14, to the foetal (18- and 24-week-old) and infant (newborn and 17-month-old) spinal cord was examined using in vitro autoradiography. Somatostatin binding sites were detected at cervical, thoracic and lumbosacral levels in foetal as well as in infant spinal cord. The radiolabelling was localized over the grey especially in the superficial layers of the dorsal horn including the substantia gelatinosa and the marginal zone. In foetal and newborn spinal cord, the direct and crossed pyramidal paths exhibited a substantial binding of the ligand. A similar labelling was not observed in the pyramidal paths of a 17-month-old child or in anencephalic newborn spinal cord or previously described in adult. These results emphasize the early presence of somatostatin binding sites during the ontogeny of the human spinal cord. Further, the transient appearance of somatostatin binding sites in the pyramidal paths, prior the myelination, raises the question whether somatostatin receptors could be involved in the maturation of certain normal paths.

Aging↗
PubMed1988

Somatostatin concentrations and binding sites in human frontal cortex are differentially affected in Parkinson's disease associated dementia and in progressive supranuclear palsy.

Somatostatin (SRIF) binding sites were characterized in membrane preparations from post mortem human brain tissues using 125I-Tyr0-D-Trp8-SRIF as a ligand. Density of binding sites were high in subiculum and cortex, moderate in temporal cortex, hippocampal formation and hypothalamus and low in putamen. No correlation was observed with the regional distribution of SRIF levels as measured by RIA. Pharmacological characterization, in frontal cortex preparations, revealed that 125I-Tyr0-D-Trp8-SRIF binding was heterogenous and fitted best with a two sites model. 125I-Tyr0-D-Trp8-SRIF binding was guanine nucleotide dependent. Cortical 125I-Tyr0-D-Trp-8-SRIF binding was not different from controls in non-demented or demented parkinsonians and in patients with progressive supranuclear palsy. On the contrary, SRIF levels were significantly decreased in demented parkinsonians.

Aged↗
PubMed1988

Evidence for a direct action of neuropeptide Y in the rat pituitary gland.

Neuropeptide Y (NPY) has recently been localized in the rat hypothalamus. In order to evaluate the putative effects of NPY on pituitary function, its action was examined on anterior pituitary cells in culture. Also, an immunocytochemical method was used with the aim of localizing endogenous NPY-like material at the cellular and subcellular levels of the pituitary gland. In vitro studies using dispersed anterior pituitary cells indicated that NPY (10(-6) to 10(-9)M) increased the secretion of luteinizing hormone, growth hormone and prolactin, whereas beta-lipotropin hormone and thyrotropin secretions were not affected. The presence of endogenous NPY was demonstrated in gonadotrophs, somatotrophs, corticotrophs and some lactotrophs, but not in thyrotrophs. In immunoreactive cells, NPY-like material was detected in the cytoplasmic matrix, in the secretory granules and in the nucleus distributed primarily in the euchromatin, in the vicinity of the heterochromatin. NPY-like immunoreactivity was also observed at the plasma membrane but only scarcely. These biochemical and immunocytochemical results indicate that NPY may play a direct regulatory role in adenohypophyseal secretion.

Animals↗
PubMed1988

Dopamine inhibits prolactin secretion stimulated by the calcium channel agonist Bay-K-8644 through a pertussis toxin-sensitive G protein in anterior pituitary cells.

In primary culture of anterior pituitary cells, BAY-K-8644, a calcium channel agonist, stimulated PRL secretion by 83% with EC50 of 18 nM. This effect was blocked by nifedipine, a calcium channel antagonist. The stimulations of PRL secretion induced by potassium (50 mM) and BAY-K-8644 were additive. Dopamine inhibited basal as well as BAY-K-8644-stimulated PRL secretion by 64% and 75%, respectively, and with respective EC50 values of 4.5 and 0.6 nM. In the presence of 50 mM K+, dopamine only partially blocks the dose-dependent stimulation of PRL secretion induced by the calcium channel agonist. The inhibitory dopamine effect was blocked by (+)butaclamol, a specific dopamine receptor antagonist. The dopamine response was also blocked by 1-sulpiride, a specific dopamine D2 receptor antagonist, and mimicked by RU 24926, a specific dopamine D2 receptor agonist, suggesting that the dopamine effect on BAY-K-8644-stimulated PRL secretion was mediated through a D2 dopamine receptor. Although unknown, the mechanism by which dopamine inhibited the BAY-K-8644-stimulated PRL secretion involves a GTP binding protein sensitive to Bordetella pertussis toxin. In fact, the dopamine inhibition of PRL secretion induced by the calcium channel agonist was blocked by the pretreatment of cells with the toxin. These results suggest that dopamine D2 receptors in lactotroph cells modulate calcium influx through a GTP binding protein.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Influence of starvation on hormonal control of hypophyseal secretion in rats.

The reduction of hypophyseal hormone secretion during starvation is not completely understood. A previous study showed that the concomitant reduction of plasma TSH and T3 may be related to an increased sensitivity of the thyrotrope cell to T3. This suggests that regulation of hypophyseal secretion by peripheral hormones may be altered in starved rats. As GH and PRL secretion are under the control of thyroid and steroid hormones, the aim of the present study was to investigate the modification of feed-back control by T3 or E2 on hypophyseal secretion during starvation. For this purpose, pituitary GH, PRL and TSH contents and their plasma responses to TRH injection were measured in euthyroid, thyroidectomized (Tx), T3-supplemented Tx and E2-treated male Wistar rats before and after a 3-day starvation. TRH (0.25 micrograms/100 g) was injected iv through a chronically-implanted catheter. Our results show that GH content and GH plasma response to TRH are dramatically increased in T3-treated Tx starved rats, suggesting that starvation also increases the effectiveness of T3 influence on somatotrope cell secretion. By contrast, effects of T3 on PRL secretion remain unchanged during starvation. Furthermore, starvation in E2-treated rats is associated with a marked rise in the PRL and GH responsiveness to TRH without any significant change of hormonal pituitary content. This suggests that, in starved rats, E2 increases the effects of TRH on lactotrope and somatotrope secretion. No significant effect on TSH secretion could be demonstrated. Thus, starvation seems to act differentially on the feed-back mechanisms controlling the hormonal secretion of the three adenohypophyseal target cells to TRH.

Animals↗
PubMed1988

Second messengers associated with the action of AII and dopamine D2 receptors in anterior pituitary. Relationship with prolactin secretion.

We have shown that DA receptors of the D2 subtype inhibit prolactin release by several mechanisms. DA receptors inhibit cyclic AMP production through a GTP binding protein sensitive to the Bordetella pertussis toxin. However, this mechanism cannot be involved in the blockade of the AII stimulated prolactin secretion by DA. This blockade is probably partly due to the inhibition of the AII-stimulated inositol phosphate production by DA. This inhibition is also sensitive to the Bordetella pertussis toxin. The toxin is able to ADP-ribosylate three substrates in anterior pituitary cells (39, 40 and 41 kDa). In addition, we show here that AII receptors inhibit adenylate cyclase of anterior pituitary cell homogenates, but not in intact cells.

Adenosine Diphosphate Ribose↗
PubMed1987

An islet activating protein-sensitive G protein is involved in dopamine inhibition of angiotensin and thyrotropin-releasing hormone-stimulated inositol phosphate production in anterior pituitary cells.

In primary culture of anterior pituitary cells, dopamine inhibited the angiotensin (AII)-stimulated inositol phosphate production by 28 +/- 2.5% (n = 14), with an EC50 of 660 +/- 228 nM (n = 8). This effect was blocked by (+)-butaclamol, a specific dopamine receptor antagonist. RU 24926, a D2 specific agonist, but not SKF 38393, a specific D1 agonist, inhibited AII-stimulated inositol phosphate production, suggesting that this dopamine effect is mediated through a dopamine receptor of the D2 subtype. Dopamine also partially inhibited (25%) inositol phosphate production stimulated by thyrotropin-releasing hormone (TRH). Our results suggest that the dopamine-mediated inhibition of hormonally stimulated inositol phosphate production is probably not mediated through the known inhibitory effects of dopamine on cAMP and Ca2+ intracellular concentrations. Although unknown, the mechanism by which dopamine inhibited the AII and TRH-stimulated inositol phosphate production implicates a GTP binding protein sensitive to the islet activating protein (IAP) since dopamine effects were blocked by this toxin. The alpha subunit of the GTP binding protein involved could be one of the three ADP-ribosylated proteins found in anterior pituitary cells in primary cultures, the alpha o (39 kDa), the alpha i (41 kDa), and an alpha subunit of 40 kDa. Indeed, we show here that this 40-kDa IAP substrate, already described in a few tissues, is present in anterior pituitary cells. The negative coupling between dopamine receptors and the AII or TRH inositol phosphate production systems, could be implicated in the dopamine inhibition of the AII- and TRH-stimulated prolactin release since such an inhibition is blocked by IAP. Our results suggest that the negative regulation of inositol phosphate production is one of the mechanisms by which dopamine controls hormonally stimulated prolactin release.

Adenosine Diphosphate Ribose↗
PubMed1987

Somatostatin receptors on cortical neurones and adenohypophysis: comparison between specific binding and adenylate cyclase inhibition.

Primary cultures of mouse embryonic neurones from the cerebral cortex and rat pituitary membranes were used to identify and characterize further the somatostatin receptors coupled to an adenylate cyclase and to compare these receptors with specific binding sites for a non-reducible somatostatin analog. 125I-CGP 23996 on both tissues. 125I-CGP 23996 bound specifically to a single population of sites on cortical neurones and pituitary membranes, with a high affinity (Kd = 2.76 and 1.95 nM respectively). The rank order of potency of somatostatin-(1-14) and some analogs (somatostatin-28, [D-Trp8,D-Cys14]somatostatin-(1-14), native CGP) to displace 125I-CGP 23996 from its binding sites was similar on both tissues. Furthermore this rank order was also found identical for the inhibition of adenylate cyclase activity on cortical neuronal and pituitary membranes. Finally a good correlation was found between the order of potencies of somatostatin analogs evaluated from binding experiments and adenylate cyclase assays, suggesting the presence of the same receptor observed under two different affinity states. According to the classification of somatostatin receptors by Tran and his colleagues (1985) these results support the hypothesis that SSA is the somatostatin receptor coupled with an adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Multiple coupling of neurohormone receptors with cyclic AMP and inositol phosphate production in anterior pituitary cells.

Regulation of adenohypophyseal hormone secretions has been shown to involve cyclic AMP production, modulation of phosphatidyl inositol diphosphate breakdown and Ca2+ mobilization. Various neurohormone receptors are positively or negatively coupled to adenylate cyclase activity in anterior pituitary cells. The effects of these neurohormones on adenylate cyclase activity are consistent with the effect on hormone secretions, suggesting that modulation of the enzyme activity is actually involved in the regulation of adenohypophyseal secretions. Thus DA inhibits, whereas VIP stimulates adenylate cyclase activity of the same cell type, which, according to the effect of these neurohormones on prolactin secretion, appear to be lactotrophs. On the other hand, SRIF inhibits, whereas GRF stimulates the adenylate cyclase activity of another cell type, namely somatotrophs, whereas CRF appears to act on a third cell type, corticotrophs. Peripheral hormones have been shown to modulate the sensitivity of anterior pituitary cells to these neurohormones. Estradiol long-term treatment has an anti-dopaminergic effect on prolactin secretion. The steroid also suppresses the dopamine inhibition of adenylate cyclase. This effect appears selective to the DA inhibition, since AII inhibition of the enzyme is only partially reduced, whereas the somatostatin inhibition is markedly increased. Peripheral hormones seem to affect the sensitivity of adenohypophyseal cells not only by modulating the number of receptors for a given neurohormone but also by interfering with the coupling mechanisms of these receptors. AII and DA inhibit the adenylate cyclase activity of lactotroph cells. The prolactin stimulation induced by angiotensin is not consistent with the effect of the peptide on adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1987

Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase.

Pharmacological characterization of somatostatin (SRIF) receptors located on somatotrophs, thyrotrophs, and lactotrophs was attempted by measuring the effects of 14 structural agonists of somatostatin (SRIF) on the inhibition of basal and GRF-stimulated GH and basal and TRH-stimulated PRL and TSH secretion. We also checked the abilities of the analogs to displace [125I]N-Tyr-SRIF binding to pituitary cell membranes and their potency to inhibit adenylate cyclase activity. There was a very good correlation (r = 0.975) between the displacement of [125I]N-Tyr-SRIF and the inhibition of adenylate cyclase activity by the analogs. The effects of the analogs on secretion of the three hormones followed the same rank order of potency. However, the active analogs displayed 2-6 times lower affinities in inhibiting PRL than GH or TSH secretions. The shift in affinity was even more pronounced in the case of the lower potency of the analogs as inhibitors of adenylate cyclase activity compared to hormone secretions. Pretreatment of the cells with pertussis toxin (100 ng/ml; 24 h) blocked SRIF inhibition of basal and GRF-stimulated adenylate cyclase activity and decreased by 83% [125I]N-Tyr-SRIF binding. It also blocked the ability of SRIF to inhibit GRF-induced GH and TRH-induced PRL and TSH secretion. However, pertussis toxin also increased GRF stimulation of GH secretion and decreased TRH stimulation of both TSH and PRL secretion. We conclude from our data that SRIF-binding sites located on the three target cells of the adenohypophysis are of a single class. These binding sites are negatively coupled to adenylate cyclase, but the inhibition of hormone secretions by SRIF cannot be explained solely through adenylate cyclase inhibition. Another mechanism of transduction must be involved in the actions of SRIF on its three pituitary target cells.

Adenylyl Cyclases↗
PubMed1986

Modifications in the cortical regional distribution of choline acetyltransferase, somatostatin and somatostatin binding sites in the normal rat and following lesion of the nucleus basalis.

The regional distribution of choline acetyltransferase activity, somatostatin levels and 125I-CGP 23996 (a somatostatin agonist analog) specific binding sites in 10 separate zones of the cerebral cortex was analyzed. The study was performed in normal rats as well as 15 days after unilateral excitotoxic lesion of the nucleus basalis. A significant correlation was found in the controls between the regional distribution of choline acetyltransferase activity and somatostatin concentrations, both most highly concentrated in the piriform and entorhinal cortex. In contrast, the regional density of 125I-CGP 23996 binding sites correlated neither with choline acetyltransferase activity nor with somatostatin levels. Unilateral lesions of the basal forebrain decreased choline acetyltransferase activity in the frontal and parietal cortex, while 125I-CGP 23996 binding decreased in frontal and occipital regions. No decrease in somatostatin content was observed. The results suggest that, in rats, cortical somatostatin receptors could be associated with cholinergic afferents from the nucleus basalis in the frontal cortex only.

Animals↗
PubMed1986

Angiotensin II and dopamine modulate both cAMP and inositol phosphate productions in anterior pituitary cells. Involvement in prolactin secretion.

Despite their opposite effects on prolactin secretion, both dopamine and angiotensin II inhibit adenylate cyclase activity in homogenates of anterior pituitary cells in primary culture. Dopamine and angiotensin II inhibition of adenylate cyclase was not additive, suggesting that both neurohormones inhibit the adenylate cyclase of the lactotroph cells. Pretreatment with Bordetella pertussis toxin (islet activator protein) completely suppressed the dopamine-induced inhibition of both adenylate cyclase and prolactin secretion. The islet activator protein also reversed the angiotensin II-induced inhibition of the adenylate cyclase activity. In contrast, angiotensin II stimulation of prolactin release was not affected by the toxin. Angiotensin II also induced a dose-dependent stimulation of inositol phosphates (250%) with an EC50 of 0.1 nM, close to that observed for prolactin secretion. Islet activator protein pretreatment did not block the stimulation of inositol phosphate production. Dopamine inhibited the angiotensin II-stimulated prolactin release and the production of inositol phosphates induced by angiotensin II. It is concluded that angiotensin II and dopamine receptors of lactotroph cells are able to modulate both cAMP and inositol phosphate production. The dopamine receptor of lactotrophs appears to be the first example of a receptor which is negatively coupled to the production of inositol phosphates.

Adenosine Diphosphate Ribose↗
PubMed1986

Somatostatin and regulation of prolactin secretion.

In addition to its classical growth hormone (GH) inhibiting action, somatostatin (SRIF) inhibits prolactin (PRL) secretion in man and rat under specific endocrine conditions. Furthermore, SRIF counteracts the thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated prolactin release from rat adenohypophysis in vitro. Two criteria are needed to demonstrate a physiological role of SRIF in PRL control: specific receptors must be present on prolactin secreting cells, and antagonization of endogenous SRIF must affect PRL secretion in vitro. In fact [125I]N--Tyr--SRIF binds to membranes not only of human GH-secreting adenomas, but also of prolactinomas. Specific binding characteristics are comparable in both cell types, but the density of sites in PRL-secreting adenomas is only one-quarter that in GH-secreting adenomas. In contrast, non-PRL-secreting chromophobe adenomas are devoid of specific binding. On the other hand, administration of SRIF antisera (SRIF-AS) affects both GH and PRL secretion in starved rats (a model in which pulsatile GH secretion is abolished); a marked increase in PRL plasma levels occurs, but the needed SRIF-AS concentration is higher than that for GH disinhibition. This demonstrates that endogenous SRIF may exert a negative control over PRL secretion, although lactotroph cells appear less sensitive to SRIF than somatotrophs. Since the apparent affinity of SRIF binding sites is similar on both GH and PRL secreting cells, at least in human tumor tissues, a lower density of SRIF receptors on PRL cells could account for this reduced responsiveness. Alternatively, different coupling mechanisms may be involved in the two cell types.

Adenoma↗