Biomedical subjects

C Denef

Publications and source records attributed to C Denef.

At least 73 records · Page 4Linked to original sources

PubMed1989

Synthesis and release of acetylcholine by normal and tumoral pituitary corticotrophs.

Incubation of cultured rat pituitary cell aggregates with [3H]choline ([3H]Chol) yielded a derivative that was identified as [3H]acetylcholine ([3H]ACh) by several criteria: 1) the [3H]Chol derivative with the highest retention time coeluted with a [14C]ACh standard in cation exchange and reverse phase HPLC; 2) cholinesterase treatment converted this derivative to a substance with the retention time of [3H]Chol; 3) two blockers of ACh production, hemicholinium and 4-[(1-naphthylvinyl)pyridinium], eliminated 3H-labeled material in the HPLC fractions with ACh retention time. Spontaneous [3H]ACh release was increased by depolarizing potassium concentrations, and both synthesis and release of ACh were increased by the glucocorticoid hormone dexamethasone. Double immunostaining of choline acetyltransferase (CAT) and, respectively, of ACTH, GH, PRL, TSH, S100, LH, and FSH in rat pituitary cells revealed that most of the CAT-immunoreactive cells were also ACTH immunoreactive. A small proportion (less than 10%) of the PRL-immunoreactive cells also showed CAT immunoreactivity, but all other cell types were negative. The immunocytochemical evidence for colocalization of CAT within the ACTH cell was strengthened by the finding of a significantly higher rate of [3H]ACh synthesis in a corticotroph-enriched cell population obtained by separating pituitary cells on a velocity sedimentation gradient. In addition, the mouse pituitary corticotropic cell line AtT20 contained CAT immunoreactivity, converted [3H]Chol to [3H]ACh, and released bioactive ACh-like material. In conclusion, the present data provide strong evidence that pituitary corticotrophs synthesize and release ACh, and that the activity of this intrapituitary cholinergic transmission system is under regulatory control.

Acetylcholine↗

PubMed1989

The glucocorticoid hormone dexamethasone reverses the growth hormone-releasing properties of the cholinomimetic carbachol.

We recently reported that dexamethasone (DEX) enhances acetylcholine (ACh) release from pituitary cell aggregates. In the present study, the effect of DEX on the GH-releasing properties of the cholinergic agonist carbachol (CCh) was investigated. Perifusion of hemipituitaries from 14-day-old rats with CCh stimulated basal GH release. CCh also increased basal GH release from organ-cultured pituitaries and from pituitary cells cultured as reaggregates, but only when the thyroid hormone T3 was supplemented to the culture medium. Pretreatment of the animals in vivo with DEX abolished the CCh-induced increase in basal GH release from hemipituitaries tested in vitro. Treatment of pituitary organ cultures and reaggregate cell cultures with DEX reversed the stimulation of basal GH release by CCh into an inhibition. CCh also inhibited isoproterenol- and GRF-stimulated GH release from DEX-treated pituitary cell reaggregates. In contrast, the responsiveness of tumoral GH3 cell aggregates to CCh was not dependent on T3 or DEX during culture. The half-maximal concentration of CCh for inhibition was significantly lower than that for stimulation (1 and 10 microM, respectively). Perifusion with CCh of DEX-treated cell reaggregates consisting of a highly enriched somatotroph population (greater than 90% GH immunoreactive cells), obtained by sequential velocity and buoyant density sedimentation of dispersed cells, also inhibited basal GH release. Pretreatment of pituitary cell reaggregates cultured in DEX-supplemented medium with pertussis toxin completely abolished the inhibition by CCh. The inhibition of GH release by CCh was not affected by the Na+ conductance blocker tetrodotoxin, the Cl- channel blocker picrotoxin, or the K+ channel blocker caesium, but was abolished by the Ca2+ channel blockers cadmium and verapamil. In conclusion, CCh is capable of both stimulating and inhibiting GH release in different pituitary in vitro assay systems; the inhibition is dependent on glucocorticoids and the stimulation on the thyroid hormone T3. The mechanism of action of the inhibition seems to involve a GTP-binding protein and most probably a decrease in calcium conductance in the somatotroph.

Animals↗

PubMed1988

A diffusion-adsorption model for the computation of the amount of hormone around a secreting cell, detected by the reverse hemolytic plaque assay.

The reverse hemolytic plaque assay enables the detection of secretion products from individual cells in cultures by visualizing the plaques formed after complement-mediated hemolysis around the secreting cells. However, the precise quantitation of the amount of secretion remains problematic. In this study we propose a computation model for estimating the spreading of the secreted molecules, based on the underlying processes of diffusion and antigen adsorption by immobilized antibodies. The translational diffusion coefficient of rat prolactin at 37 degrees C, determined by laser light scattering, was 9.89 x 10(-7) cm2/s. The time-dependent concentration distribution around a constantly secreting cell in a flat quasi infinite layer, was derived from the diffusion equation, using an analytical approach based on Laplace transformation. The relations between plaque size, incubation time and secretion level were expressed as a function of the threshold concentration of secretion product that can be detected and the effective diffusion coefficient, taking antigen adsorption into account. We obtained very good agreement between observed and predicted results for plaque formation by dispersed prolactin secreting cells of 14-day-old female rat pituitaries. This study confirms the validity of the assumptions underlying the reverse hemolytic plaque assay, provided that the cell density is low, the incubation time is moderately long and the concentration of specific antiserum is sufficiently high.

Adsorption↗

PubMed1988

Enhanced ANG II activity in anterior pituitary cell aggregates from hypertensive rats.

Pituitary cell reaggregates from 14-day-old and adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were cultured in serum-free, chemically defined medium supplemented with the thyroid hormone triiodothyronine and the glucocorticoid dexamethasone. After 1 wk in culture, aggregates were transferred into a perifusion system, and the effect of angiotensin II (ANG II) on prolactin (PRL) and growth hormone (GH) release was studied. In aggregates from adult SHR, ANG II displayed a significant and dose-dependent GH releasing activity, whereas a negligible effect or no effect was seen in aggregates from adult WKY. In contrast, no difference in the stimulation of PRL release by ANG II was found. To exclude the possibility that the enhanced GH responsiveness was secondary to longstanding hypertension, aggregates from animals in the prehypertensive stage were studied. Both the GH and PRL responses to ANG II were significantly higher in aggregates from 14-day-old SHR than in aggregates from 14-day-old WKY. These data indicate that abnormal GH and PRL responses to ANG II exist in pituitary cell aggregates from SHR long before hypertension develops. Because these differences were found in pituitary cells maintained in culture for 1 wk, they do not seem to be secondary to changes in brain regulation of pituitary function but rather are caused by factors intrinsic to the pituitary.

Angiotensin II↗

PubMed1988

Stimulation and inhibition of pituitary growth hormone release by angiotensin II in vitro.

Rat pituitary cell aggregates cultured in serum-free chemically defined medium, single cells, and hemipituitaries were used in a perifusion system to study the influence of angiotensin II (AII) on GH release. In aggregates the peptide displayed both stimulatory and inhibitory effects on GH release, depending on the hormonal conditions of the culture medium and the age of the animal. When cultured in the absence of glucocorticoid, a modest but statistically significant stimulation was seen in aggregates from immature as well as adult animals. In aggregates from 5-day-old animals, dexamethasone (DEX) strongly enhanced the GH-releasing activity of AII in a dose-dependent way; in aggregates from 14- and 25-day-old rats, the same pattern was found, although the stimulatory action was weaker than the effect in 5-day-old rats. In aggregates from adult animals, the glucocorticoid established an inhibitory effect of AII on GH release, an effect seen with both low and high concentrations of DEX. These age- and DEX-dependent effects were not found for AII stimulation of PRL release. In the presence of DEX, AII also inhibited GRF-induced GH release in aggregates from adult animals, while it was synergistic with GRF in aggregates from developing animals. The effects of AII on GH release disappeared when aggregates were redispersed into single cells. However, in these single cell preparations AII strongly stimulated PRL release. In hemipituitaries from 1-, 5-, and 14-day-old animals, AII also stimulated GH release, but no effect was seen in hemipituitaries from 25-day-old and adult animals. These data indicate that AII has dual effects on GH release depending on the developmental stage of the animal and the hormonal environment. Furthermore, since no effect of AII was seen after redispersion of aggregates into single cells, both stimulatory and inhibitory effects seem to be based on an intercellular signaling system.

Angiotensin II↗

PubMed1988

Immunocytochemical and pharmacological evidence for an intrinsic cholinomimetic system modulating prolactin and growth hormone release in rat pituitary.

Pituitary cells were cultured as three-dimensional reaggregates in serum-free chemically defined medium supplemented with different concentrations of dexamethasone. Immunostaining of the cells using a polyclonal antiserum and three monoclonal antibodies raised against choline acetyl transferase (CAT), revealed the presence of CAT immunoreactivity in 4-10% of anterior pituitary cells depending on the antibody used. CAT immunoreactivity was also found in freshly dispersed anterior pituitary cells. CAT-immunoreactive cells could be enriched on BSA and Percoll gradients and codistributed with ACTH-immunoreactive cells in these gradients. Perifusion of the aggregates with the potent muscarinic receptor antagonist atropine (Atr) resulted in a dose-dependent (0.1-100 nM) increase in both basal PRL and GH secretion; the response was dependent on the dexamethasone concentration in the culture medium. A similar response to Atr was observed in organ-cultured pituitaries. The specificity of the Atr effect was supported by the findings that the potent and highly specific muscarinic receptor blocker dexetimide showed a similar action, whereas its inactive enantiomer levetimide and the nicotinic receptor blocker hexamethonium failed to do so. Two other muscarinic antagonists, benzatropine and pirenzepine, showed a dose-dependent hormone-releasing action similar to that of Atr, but were less potent than the latter. Pirenzepine was only effective at high molar concentrations, suggesting that an M2 muscarinic receptor subtype was mediating the present phenomenon. Atr also potentiated GH release stimulated by the beta-adrenergic agonist isoproterenol and PRL release stimulated by vasoactive intestinal peptide, but had no effect on GRF-stimulated GH release. The choline uptake blocker hemicholinium abolished the effect of Atr on GH and PRL release. These data suggest that certain pituitary cells can express CAT activity and that these cells exert a tonic inhibitory activity on GH and PRL release which is mediated by a cholinomimetic substance, possibly acetylcholine, through a muscarinic receptor.

Acetylcholine↗

PubMed1987

Alpha-adrenergic stimulation of growth hormone release in perifused rat anterior pituitary reaggregate cell cultures.

It has been previously shown that beta-adrenergic agonists stimulate growth hormone (GH) release from perifused rat anterior pituitary cell aggregates cultured in serum-free defined medium for 5-6 days. The present data show that the natural beta-agonist epinephrine (EPI) stimulates GH release through an additional alpha-adrenergic mechanism. The involvement of this mechanism was suggested by the following findings. The intrinsic activity of EPI, at concentrations greater than 10 nM, was significantly higher than that of isoproterenol (ISO) in stimulating GH release. Phenylephrine (PHE), a specific agonist of alpha 1-adrenergic receptors, provoked a significant rise of GH release. The effect was concentration dependent between 100 nM and 10 microM. The stimulatory effect of EPI and PHE was lowered, respectively blocked, by low concentrations of the potent alpha 1-adrenergic antagonist prazosin. The EPI-induced GH release could be totally blocked only by administration of both alpha- and beta-receptor antagonists. Under the same conditions and using concentrations up to 1 microM, the alpha 2-agonist clonidine had no or only a slight stimulatory effect; dopamine had no effect. Administration of both PHE and ISO resulted in a more than additive stimulation of GH release. The effectiveness of PHE but not clonidine, together with the high potency of the alpha 1-blocker prazosin suggest that the alpha-adrenergic receptor is predominantly of the alpha 1-subtype. When tested on days 1, 3, 6 and 8 in culture, both alpha- and beta-adrenergic responses appeared to be higher in the presence of the glucocorticoid dexamethasone compared to the responses in the absence of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Evidence that stimulation of growth hormone release by epinephrine and vasoactive intestinal peptide is based on cell-to-cell communication in the pituitary.

Epinephrine (Epi) evoked a strong concentration-dependent (1-1000 nM) rise of GH release from perifused rat anterior pituitary cells cultured as aggregates in a serum-free defined culture medium. Dexamethasone (Dex), added to the culture medium, enhanced the secretory response to Epi. Aggregates of pituitary cells separated by gradient sedimentation at unit gravity widely differed in responsiveness to Epi, provided Dex was added to the culture medium. The poorest response was seen in aggregates composed of a population highly enriched in large somatotrophs from adult male rats even when cultured in the presence of 80 nM Dex. However, when these large somatotrophs were coaggregated with various somatotroph-poor cell populations, all of which were enriched in lactotrophs, the GH response to Epi increased by a factor of 3-4. The latter populations also enhanced GH secretion stimulated by vasoactive intestinal peptide (1-10 nM). In contrast, the GH response to rat GH-releasing factor (GRF, 0.01-0.1 nM) was not significantly potentiated in the coaggregates. The facilitation of the GH response to Epi was not seen when Dex was omitted from the culture medium. All of the lactotroph-enriched populations enhancing the response to Epi also contained corticotrophs, but none were highly enriched in the latter cell type. The magnitude of the Epi effect on GH release was not affected when the large somatotrophs were coaggregated with enriched populations of gonadotrophs, thyrotrophs, or folliculostellate cells. However, coaggregation with GH3 tumor cells provoked some stimulation. The present data suggest that GH release stimulated by Epi is modulated by facilitatory interactions of somatotrophs with other cells, the latter being most likely lactotrophs, although participation of corticotrophs in this interactions cannot be unequivocally excluded. Facilitatory interactions also modulate GH secretion in response to vasoactive intestinal peptide, but the GH response to GRF weakly, if at all.

Animals↗

PubMed1987

Evidence for functional communication between folliculo-stellate cells and hormone-secreting cells in perifused anterior pituitary cell aggregates.

Dispersed anterior pituitary cells from adult female rats were separated by gradient sedimentation at unit gravity. The small-sized cell population on top of the gradient consisted of 65.6 +/- (SE) 4.2% (n = 8) cells immunoreactive to antiserum against S-100 protein, a marker of folliculo-stellate (FS) cells in rat pituitary. The corresponding fraction derived from adult male or immature female rats were also enriched in S-100 positive cells but to a lower extent. Only small numbers of S-100 positive cells were found in medium- and large-sized cell populations. Coaggregating the S-100 cell-enriched populations from adult females with other pituitary cell populations resulted in a clear-cut inhibition of the GH response to rat GH-releasing factor and beta-adrenergic agents, of the PRL response to TRH and angiotensin II (AII) and the LH response to LHRH. The magnitude of inhibition increased with the number of FS cells put into the coaggregates. In perifused aggregates prepared from different gradient fractions from immature females, there was a negative correlation between the occurrence of FS cells and the magnitude of the PRL response to AII. The low responsiveness to AII in FS cell enriched aggregates was not abolished when these aggregates were redissociated into single cells. It is suggested that FS cells constitute an intercellular messenger system for local inhibitory control of pituitary hormone secretion which is not based on direct and intimate contact between the interacting cells.

Aging↗

PubMed1986

The prolonged action of the LHRH agonist buserelin (HOE 766) may be due to prolonged binding to the LHRH receptor.

Hemi-pituitary glands of ovariectomized rats were superfused for 4 h with either LHRH or the analog buserelin (HOE 766) at several concentrations, and thereafter with medium only for another 1.5 h. In a further experiment glands were exposed for 2.5 h to LHRH or buserelin at a single concentration (5 ng/ml) and subsequently for another 2.5 h to either the same agonist (LHRH or buserelin) alone (5 ng/ml), the agonist plus an LHRH-antagonist (ORG 30093, 1000 ng/ml), the LHRH- antagonist alone, or medium alone. LHRH and buserelin stimulated gonadotropin release equally well. After cessation of this stimulation, the gonadotropin release by the buserelin-treated pituitary glands and the glands, treated with the highest dose of LHRH (1000 ng/ml), continued, while the release by the glands, treated with the lower doses of LHRH, declined. The LHRH-antagonist completely blocked the release of LH, stimulated by buserelin or LHRH, as well as the prolonged activation of the release, caused by buserelin pre-treatment. In a superfusion experiment with pituitary cell aggregates of 14-day-old intact female rats, buserelin stimulated the release of LH much more effectively than LHRH itself. Moreover, the release caused by buserelin declined more slowly after cessation of the stimulation. Finally, in a pituitary cell monolayer culture the Kd's of LHRH, buserelin and the antagonist were determined as 4.7 X 10(-9) M, 2.4 X 10(-10) M and 4.6 X 10(-9) respectively. It was concluded that the estimates of the potencies of LHRH and buserelin depend on the choice of the test-system. It is suggested that the long duration of action of buserelin is at least partly due to prolonged binding to the LHRH-receptor.

Animals↗

PubMed1986

Characterization of luteinizing hormone-releasing hormone receptor binding in rat pituitary cell monolayer cultures; influence of intercellular communication.

Receptors for the luteinizing hormone-releasing hormone (LHRH) were characterized in rat pituitary cells cultured for 3 days as monolayers on coverslips using 125I-[D-Ala6-Pro9-LHRH-NEt] as the labeled ligand. The monolayers were left intact during the binding assay. Specific binding displayed the various characteristics of binding to the physiological LHRH receptor. Various kinetic data corresponded to those reported previously. However, in these cultured cells, in which binding was tested in a physiological medium, the dose response of competition for binding by LHRH agonists ranged over a smaller concentration range (less than 2 orders of magnitude) than that by LHRH antagonists. In a cation-free buffer competition curves of agonists and antagonists were parallel but the apparent dissociation constant was lower than in the physiological medium. In cultures of pituitary cell populations separated by unit gravity sedimentation, the specific binding increased with the proportional number of gonadotrophs in the various populations. However, when the gonadotroph-richest population (approximately equal to 70% gonadotrophs) was cultured after recombination with gonadotroph-poor populations, binding capacity significantly increased. Microscopic examinations suggested that this phenomenon was the consequence of disrupting cellular contacts among gonadotrophs. It is concluded that certain characteristics of LHRH receptors tested on cells in a tissue-like organization and in a physiological environment are different from those reported previously in disrupted cells or monodispersed cell suspensions and that intercellular communication is an important factor controlling LHRH receptors.

Animals↗

PubMed1986

Paracrine interactions in the anterior pituitary.

The topographical affinity between certain cell types in rat anterior pituitary as well as the presence of biogenic amines, neuropeptides, growth and tissue factors in specific cell types suggest participation of paracrine control mechanisms in the regulation of anterior pituitary hormone secretion. Due to the recent advances in the separation of pituitary cell types and the development of three-dimensional cell cultures, direct experimental evidence for control by intercellular messengers has become available. The stimulation of PRL release from superfused pituitary cell aggregates by LHRH has been shown to be mediated by gonadotrophs. Gonadotrophs appear to secrete a factor with PRL-releasing activity. Gonadotrophs also modulate the stimulation of PRL release by angiotensin II. Interaction of somatotrophs with an unknown small-sized cell type strongly amplifies the GH response to adrenaline, GRF and VIP. The latter phenomenon requires the permissive action of glucocorticoids. Some of these in vitro observations can be correlated with recently reported in vivo actions of LHRH, PRL and angiotensin II and with pathophysiological changes in the pituitary.

Angiotensin II↗

PubMed1985

Beta-adrenergic stimulation of adenosine-3',5'-monophosphate (c-AMP) accumulation and of prolactin and growth hormone secretion in rat anterior pituitary cell cultures.

The beta-adrenergic agonist 1-isoproterenol (ISO) (10(-9)-10(-7) M) provoked a prompt and profound increase of intracellular c-AMP accumulation in monolayer cultures of rat anterior pituitary. In superfused reaggregate cell cultures ISO also stimulated c-AMP outflow. The effect was blocked by propranolol and the highly selective beta 2-receptor blocker ICI 118.551. Epinephrine (E), norepinephrine (NE) and the highly selective beta 2-agonist zinterol (ZIN) also stimulated c-AMP accumulation. The order of potency ZIN greater than or equal to ISO greater than E much greater than NE together with the high potency of ICI 118.551 suggests the beta-effect is mainly through the beta 2-receptor subtype. The same concentrations of ISO strongly stimulated growth hormone (GH) release and, as previously shown, prolactin (PRL) release from superfused reaggregate cell cultures, but not luteinizing hormone or thyroid stimulating hormone release. Stimulation of PRL and GH release from these cultures was also induced by the adenylyl cyclase activator forskolin. Since interference of beta-adrenergic effects on contaminating fibroblasts or endothelial cells could be reasonably excluded, the present data suggest that beta-adrenergic stimulation of c-AMP accumulation in anterior pituitary cells elicits GH and PRL release.

Animals↗

PubMed1985

Beta-adrenergic stimulation of adenosine-3',5'-monophosphate (c-AMP) in primary cultures of rat anterior pituitary cell populations separated by unit gravity sedimentation. Relationship to growth hormone and prolactin release and to nonsecreting cells.

The effect of the beta-adrenergic agonist isoproterenol (ISO) on c-AMP accumulation and on growth hormone (GH) and prolactin (PRL) release was studied in primary cultures of anterior pituitary cell populations with different proportional number of somatotrophs and lactotrophs, obtained by velocity sedimentation at unit gravity. ISO stimulated c-AMP levels in highly-enriched lactotroph (approximately 70%) as well as in highly-enriched somatotroph (approximately 65%) populations. ISO-stimulated c-AMP accumulation was attenuated by dopamine (DA) in highly enriched lactotroph but not somatotroph populations. In a small-cell population consisting of a much lower proportional number of lactotrophs and somatotrophs, the proportional increase of c-AMP accumulation was several times higher than in the other populations and the effect was not suppressible by DA. In this small-cell population, GH but not PRL release was more responsive to ISO than in the other populations. The present observations are consistent with the interpretation that the changes in c-AMP levels induced by ISO originate in part in somatotrophs and lactotrophs. However, the present data also demonstrate that the most responsive cell population in terms of c-AMP accumulation consists of small cells. The majority of these cells could not be identified. The possibility that these cells may be nonsecreting folliculostellate cells is discussed.

Animals↗

PubMed1985

Stimulation of growth hormone release by vasoactive intestinal peptide and peptide PHI in rat anterior pituitary reaggregates. Permissive action of a glucocorticoid and inhibition by thyrotropin-releasing hormone.

In superfused rat anterior pituitary cell reaggregates, cultured for 5 days in serum-free defined medium, vasoactive intestinal peptide (VIP) concentration-dependently stimulated prolactin (Prl) release but had only a marginal effect on growth hormone (GH) release. When reaggregates were cultured in the presence of 80 nM dexamethasone (Dex) VIP strongly stimulated GH release from a concentration as low as 0.1 nM. VIP did not stimulate LH release. Peptide PHI also stimulated GH release but thyrotropin-releasing hormone (TRH) or angiotensin II did not. In fact, TRH slightly but transiently inhibited basal GH release and strongly inhibited VIP-stimulated GH release. GH-releasing factor (GRF) stimulated GH more potently and with higher intrinsic activity than VIP but GRF did not increase Prl release. The present data indicate that under defined hormonal conditions VIP and PHI are capable of stimulating GH release and that TRH can antagonize this effect by a direct action on the pituitary.

Animals↗

PubMed1985

Regulation of prolactin release by angiotensin.

In superfused anterior pituitary cell aggregates, prolactin release is stimulated by angiotensin II (AII) in a concentration-dependent fashion between 0.1 and 10 nM. When studied in aggregates prepared from pituitary cell populations separated according to size by unit gravity sedimentation, the PRL response to AII was weak in a population enriched in lactotrophs but deprived of gonadotrophs. In other separated populations, the response increased with the proportional number of gonadotrophs. The response also increased when lactotrophs were co-aggregated with an enriched population of gonadotrophs. It is proposed that the PRL response to AII is augmented by an intercellular messenger system presumably operating between gonadotrophs and lactotrophs.

Angiotensin II↗

PubMed1984

Stimulation of spontaneous and dopamine-inhibited prolactin release from anterior pituitary reaggregate cell cultures by angiotensin peptides.

In superfused anterior pituitary reaggregate cell cultures angiotensin II (AII) stimulated both spontaneous and dopamine-inhibited prolactin (PRL) release from subnanomolar concentrations. Angiotensin I (AI) and angiotensin III (AIII) also stimulated PRL release. The magnitude and rate of response to AI was equal to or only slightly lower than that to AII. However, the angiotensin converting enzyme (ACE) inhibitors captopril and teprotide (1 microM) completely abolished the PRL response to 0.1 nM AI and strongly reduced that to 1 nM AI. The intrinsic activity of AIII was lower than that of AII but could be enhanced by adding 2 microM of the aminopeptidase inhibitor amastatin to the superfusion medium. After withdrawal of AIII, PRL secretion rate rapidly returned to baseline levels, whereas after withdrawal of AI or AII, secretion fell to a level remaining significantly higher than basal release. The present findings indicate that stimulation of PRL release by AI is weak unless it is converted into AII by ACE and that aminopeptidase may be important in determining the magnitude and termination of the PRL response. Furthermore, the active peptides induce a different pattern of response.

Angiotensin I↗

PubMed1984

Beta 2-receptors in the rat anterior pituitary mediate adrenergic stimulation of prolactin release.

As previously shown, the beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine stimulate prolactin (PRL) release from superfused rat anterior pituitary cell aggregates. In order to further characterize the beta-adrenergic response in this tissue preparation, the effects of various beta-adrenergic agents were investigated. The beta 2-agonist, zinterol, stimulated PRL release at concentrations more than 4 orders of magnitude lower than prenalterol, a beta 1-agonist with high potency in rat heart. The order of potency of the antagonists IPS 339 (beta 2), ICI 118.551 (beta 2), propranolol, sotalol, practolol (beta 1), metoprolol (beta 1) and H 35/25 for inhibition of beta-agonist-stimulated PRL release provided additional support for a beta 2-stimulatory effect. beta-Agonists were also capable of stimulating PRL release from superfused intact pituitaries. The beta-adrenergic response desensitized rapidly during prolonged exposure of the aggregates to beta-agonists.

Adrenergic beta-Agonists↗