Biomedical subjects

F Peillon

Publications and source records attributed to F Peillon.

At least 37 records · Page 2Linked to original sources

PubMed1994

Immunohistochemical localization of different laminin isoforms in human normal and adenomatous anterior pituitary.

BACKGROUND: Laminin (LM) is an integral component of basement membranes (BM), with important roles in various aspects of cell biology. Several different isoforms of LM have been described, and each comprises a molecule consisting of three subunit polypeptides, the A, B1, B2, M or S chain. EXPERIMENTAL DESIGN: The distribution of different LM subunits was studied in human nontumoral anterior pituitaries obtained postmortem and in pituitary adenomas by immunocytochemical methods using specific monoclonal antibodies. RESULTS: In normal tissue, the A, B1, and B2 chains had a ubiquitous localization in both parenchymatous and vascular BMs and in the pericapillary connective tissue space also. The S chain seemed to have principally a vascular localization, in contrast to the M chain that was mostly localized in the parenchymatous BM. The same antigens were investigated in 23 human pituitary adenomas of different secretory type, grade and invasiveness. In all cases, the five monoclonal antibodies gave a positive staining. The presence or the localization of LM chains did not display a specific pattern in the adenomas according to their secretory type, grade or extent of local invasion. In the adenomas, the anti-A, -B1, and -B2 monoclonal antibodies stained the stroma and in particular the vascular BMs as well as the sparse elements of parenchymatous BMs when they were present. The staining with anti-S antibody was localized in the stroma and around all the blood vessels. In contrast, the immunoreactive material to anti-M antibody was associated to the sparse fragments of parenchymatous BMs and it delineated the boundary of adenoma cells and stroma. Within the stroma, the anti-M antibody immunoreactivity was regularly associated with the arterial walls but rarely with the venule walls. CONCLUSIONS: The human normal and tumoral anterior pituitary express all five LM subunits and thus contain several LM isoforms with different patterns of localization. The most striking difference between the human normal and tumoral anterior pituitary concerns the peculiar expression of LM isoforms by adenomatous neovessels.

Adenoma↗

PubMed1993

Presence and characterization of the somatostatin precursor in normal human pituitaries and in growth hormone secreting adenomas.

Normal and tumoral human pituitaries release in vitro SRIH and contain messenger RNAs encoding preproSRIH. In the present study, we document the presence and characterization of the SRIH precursor in both human normal pituitaries and in GH-secreting adenomas. Molecular sieve filtration of normal pituitary and adenoma acid extracts revealed the presence of three immunoreactive SRIH peaks, distinct from SRIH 1-28 and SRIH 1-14. Western blot analysis performed under both nonreducing and reducing conditions confirmed the presence of the three different immunoreactive forms with respective molecular masses estimated as 21, 17, and 12 kilodaltons. When analyzed in reverse phase high performance liquid chromatography, the three immunoreactive SRIH material contained in the three peaks coeluted with the proSRIH extracted from rat hypothalamus and from a neuroblastoma cell line (N2A) transfected with the human preproSRIH complementary DNA. None of these three forms could bind concanavalin A. Digestion of the three forms with a specific endopeptidase resulted in the generation of SRIH 1-14, indicating that they can be considered as SRIH precursor or related forms. Estimation of proSRIH amount after molecular sieve filtration indicated that normal human pituitaries (n = 4) contained proSRIH in variable amounts (from 26.5-303 pg/mg proteins), the 21-, 17-, and 12-kilodalton forms being always present, in addition to SRIH 1-28. In contrast, among the 21 adenomas tested, only 11 contained proSRIH material (from 9-4480 pg/mg proteins). Moreover, neither SRIH 1-28 nor SRIH 1-14 could be detected in these adenomas. These data demonstrate the presence of high molecular mass SRIH in normal pituitaries which represent unprocessed proSRIH material. This provides an additional argument for a local synthesis of SRIH. Additionally, the fact that only 50% of GH-secreting pituitary adenomas here studied contain exclusively proSRIH may reflect an alteration in messenger RNA translation or in proSRIH processing, or both, resulting in the absence of mature SRIH in these adenomas.

Adenoma↗

PubMed1993

Invasive human pituitary tumors express a point-mutated alpha-protein kinase-C.

Protein kinase-C (PKC) is a ubiquitous eukaryotic kinase that plays a key role in transmembrane signaling and influences important cellular processes, such as proliferation. Increases in its activity and expression have been demonstrated in adenomatous human pituitaries, with protein expression being the highest in invasive tumors (1). Moreover, in these same invasive tumors, the mean increase in expression (8.9-fold) does not correlate with the mean increase in activity (2.6-fold), suggesting a dysfunction in PKC in these tumors. Here, we show that the PKC alpha-isoform (alpha PKC) is overexpressed in human pituitary tumors. The complete sequencing of the PKC cDNA from four invasive tumors has revealed a point mutation that is absent in the noninvasive tumors analyzed. The point mutation is located at position 294 of the protein, in the V3 region, leading to a substitution of a negatively charged aspartic acid by an apolar glycine. Thus, not only is alpha PKC overexpressed in human pituitary tumors, but it is also structurally altered in the invasive subpopulation of these tumors.

Amino Acid Sequence↗

PubMed1993

Somatostatin receptors, adenylate cyclase activity, and growth hormone (GH) response to octreotide in GH-secreting adenomas.

To determine the cellular mechanism(s) of the variability in GH responsiveness to octreotide in acromegaly, somatostatin (SRIH) receptor status was studied in 37 GH-secreting adenomas. SRIH receptor binding was always present in all GH-secreting adenomas either in membrane preparations (Exp A; n = 17) or by quantitative autoradiography (Exp B; n = 20). In membranes, maximal binding capacities ranged from 83-2331 fmol/mg protein; affinity was in the nanomolar range (Kd, 1.3 +/- 0.2 nmol/L). By quantitative autoradiography, SRIH-14 and octreotide were equally active in displacing [125I]SRIH binding in tumors (Spearman correlation rho = 0.92). IC50 values ranged from 3-22 nmol/L (mean +/- SE, 8.0 +/- 1.3 nmol/L). In Exp A, basal adenylate cyclase (AC) activity was high in 7 tumors (841 +/- 306 pmol/L cAMP x 30 min/mg protein) compared to that in the other 10 (252 +/- 92 pmol/L cAMP x 30 min/mg protein). In these 7 tumors, GH-releasing hormone (0.1 mumol/L) stimulation of AC was lower (53 +/- 11% vs. 297 +/- 48%), whereas SRIH (1 mumol/L) inhibition was higher (52 +/- 5% vs. 34 +/- 5%). Similar results were obtained with Exp B tumors. In both experiments, no correlation was apparent between SRIH-binding capacity and inhibition of AC. In Exp B, a variable decrease in mean plasma GH levels was observed (> or = 80% in 5 patients, between 50-80% in 8 patients, and < or = 50% in 5 patients) after a single sc injection of octreotide (100 micrograms). A modest correlation was found between the GH response to octreotide and SRIH-binding capacity (rho = 0.48) or SRIH inhibition of AC (rho = 0.61). The IC50 values to displace SRIH binding were lower in poorly responsive patients than in highly responsive ones (IC50, 4.6 +/- 1.9 and 13.9 +/- 2.7 nmol/L, respectively). These data indicate that an absence of SRIH receptors cannot account for the weak response to SRIH therapy in 20-30% of acromegalic patients. Alternatively, the weak correlation between either SRIH binding or SRIH inhibition of AC with octreotide inhibition of plasma GH levels might reflect the heterogeneity of SRIH receptor subtypes in GH-secreting adenomas.

Adenoma↗

PubMed1992

Evidence of tyrosine hydroxylase mRNA in the anterior and neurointermediate lobes of female rat pituitary.

The anterior pituitary is thought to be unable to synthesize dopamine (DA) except under experimental conditions where a tyrosine hydroxylase (TH) activity, the rate-limiting step of its synthesis, has been demonstrated. In this work, we tested whether the enzyme described as active under particular conditions comes from de novo TH gene transcription or from a pre-existing TH mRNA poorly translated or untranslated under physiological conditions. Therefore, we searched for the presence of TH mRNA in normal female rat pituitary using the polymerase chain reaction following reverse transcription (RT/PCR) and in situ hybridization (ISH). The neurointermediate lobe (NIL) of the hypophysis was used as negative tissue, since it is thought to be unable to synthesize TH. As expected, no ISH labelling could be seen in the neural lobe (NL). However, scarce labelled cells were found in the intermediate lobe (IL) confirming the positive results observed in the NIL by RT/PCR. The anterior lobe (AL) also presented TH mRNA by PCR and ISH. The TH gene expression in sparse cells of the AL is discussed in regard to the ability of the AL to synthesize DA under particular conditions from a pre-existing mRNA.

Animals↗

PubMed1992

Immunoreactive thyroliberin (TRH) precursor forms in human hypothalamus and anterior pituitary tissues.

Immunoreactive (IR) proTRH forms were characterized in human hypothalamic tissue with two antisera raised against a hepta- and a decapeptide containing the TRH progenitor sequence (-Gln-His-Pro-Gly-). A similar study was performed in human normal and adenomatous anterior pituitaries, tissues in which TRH synthesis has been previously suggested. IR-proTRH was found in all the samples ranging from 42-775 fmol/mg proteins. Size exclusion chromatography identified a major 25-35 kDa form and a minor 4-8 kDa form. The existence of the major form was confirmed by immunoblotting. The results suggest that both human hypothalamic and normal or adenomatous anterior pituitary tissues synthesize similar IR-proTRH forms.

Adenoma↗

PubMed1992

Detection of thyrotropin-releasing hormone (TRH) mRNA by the reverse transcription-polymerase chain reaction in the human normal and tumoral anterior pituitary.

To investigate the presence of TRH mRNA in the human anterior pituitary tissue, total RNA from human normal and tumoral anterior pituitary, hypothalamus (positive control) and muscle tissues (negative control) was reverse transcribed (RT) to the first strand of cDNA. RT products were then amplified by polymerase chain reaction (PCR) using a set of three exon-specific primers (two external 5' and 3' primers and one internal 3' primer) for a target sequence of the TRH gene including an intronic sequence of about 650 base pairs (bp). Southern analysis of the RT-PCR products specifically hybridizing with a 45-mer TRH probe showed two bands of the predicted sizes (399 and 351 bp) far more intense in hypothalamus than in normal and tumoral anterior pituitary tissue. The 399 and 351 bp RT-PCR products contained the BglII enzyme restriction site included in the TRH cDNA sequences spanned by the primers and the two respective digested fragments which were, as predicted, 337 and 289 bp long, hybridized with the TRH probe. Based on these results, we can conclude that the RT-PCR products generated from RNA tissue were the target TRH sequences in the human normal and tumoral anterior pituitary tissue as well as in the hypothalamus. Our data imply TRH gene expression in the human anterior pituitary.

Adenoma↗

PubMed1992

Somatostatin cells in human somatotropic adenomas.

Data from our group have shown that the human adenomatous and normal anterior pituitary may be the source of somatostatin (SRIH). SRIH-producing cells were identified in two somatotropic adenomas. Immunoreactive SRIH cells were present in both cases. In case 2, material was available for RNA studies, in situ hybridization and electron microscopy. The size of the transcript identified by Northern blot analysis was identical to that of hypothalamic SRIH mRNA. In situ hybridization showed that the SRIH gene was expressed in a cell subset superimposable to that identified by immunocytochemistry. Co-localization studies revealed that SRIH and growth hormone (GH) immunoreactivities were not present in the same cells. Ultrastructural immunogold labelling showed that SRIH cells had features distinct from those of the somatotropes. The results confirm that the somatotropic adenomas have the ability to synthesize SRIH, indicate that SRIH expression is restricted to a subset of adenoma cells different from GH-producing cells, and imply that SRIH cells are involved in paracrine regulation of neighbouring somatotropes.

Adenoma↗

PubMed1992

Specific alterations of the basement membrane and stroma antigens in human pituitary tumours in comparison with the normal anterior pituitary. An immunocytochemical study.

Our report is the first immunocytochemical study of the principal elements of the basement membrane (BM) and connective tissue in normal and adenomatous human anterior pituitaries. In normal tissues, both the parenchymatous BM limiting the endocrine cell cords and the endothelial BM around the capillaries were continuous and were stained with anti-laminin (LM), anti-type IV collagen (CIV) and anti-fibronectin (FN) antisera. Antiserum to type I collagen (CI) stained the connective tissue only. The same antigens were investigated in 23 human pituitary adenomas, 6 of them having been diagnosed as locally invasive by the radiologist and the neurosurgeon. In all cases a lack of cordal structure was observed and the parenchymatous BM was completely absent (9 cases) or fragmented (14 cases). No correlation could be established between the extent of parenchymatous BM alterations and the invasive behaviour of the tumour. In contrast, a continuous endothelial BM was observed around the blood vessels in all cases and its presence was confirmed in double immunofluorescence experiments using anti-von Willebrand factor and anti-LM or anti-CIV antisera. Anti-FN and CI also stained the wall of the vessels. The tumours showed arterial development, in addition to the capillaries found in normal tissue. The present results favour the hypothesis of a decreased synthesis of parenchymatous BM by human adenomatous pituitary cells in comparison with normal cells and show that these tumours are the site of an active arterial neovascularization.

Adenoma↗

PubMed1992

Resistance to somatostatin (SRIH) analog therapy in acromegaly. Re-evaluation of the correlation between the SRIH receptor status of the pituitary tumor and the in vivo inhibition of GH secretion in response to SRIH analog.

The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated (> 10 micrograms/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the alpha subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (G alpha s). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1992

Autocrine and paracrine effects of peptides on human pituitary cells.

In contrast to normal human pituitaries, GH-secreting adenomas cannot process in vivo ProSRIH whereas they do it in vitro. The existence of an endogenous factor able to inhibit ProSRIH processing in vivo was postulated and such a role was analyzed for GHRH. Results showed that when GH adenomas are incubated in vitro with GHRH 10(-8) M, their ProSRIH contents are decreased, percent inhibition being negatively correlated to the amount of endogenously released GHRH. When incubation is performed in the presence of GHRH antibody in order to block the effect of endogenous GHRH, Pro-SRIH content is increased. The same effects are observed on SRIH release: inhibition by GHRH, stimulation by GHRH antibody. Normal rabbit serum had no effect. It may therefore be concluded that the absence of ProSRIH maturation observed in adenomas in vivo may be the consequence of the GHRH release that is known to be higher from GH adenomas than from normal pituitaries.

Adenoma↗

PubMed1992

Evidence of gonadotropin-releasing hormone mRNA in the rat anterior pituitary.

We have previously reported the presence and the persistence of immunoreactive GnRH cells in the rat anterior pituitary in the absence of exogenous GnRH. To substantiate the hypothesis of its endogenous production, we have investigated the presence of GnRH mRNA in rat anterior pituitary tissue using a reverse transcription-polymerase chain reaction (RT-PCR) amplification protocol. Total RNA from rat anterior pituitary, hypothalamus (positive control), and muscle (negative control) was reverse transcribed to the first strand of cDNA and amplified by PCR using a set of three exon-specific primers for a target sequence of the GnRH gene, i.e. two external 5' and 3' primers and one internal 3' primer. UV light analysis of the size-fractionated RT-PCR products showed two bands of the predicted sizes [511 and 397 base pairs (bp)] hybridizing with GnRH probes in Southern analysis only in hypothalamus and in anterior pituitary but not in muscle. These two bands were far more intense in the hypothalamus than in the anterior pituitary. Restriction enzyme analysis evidenced that the two RT-PCR products included the HindIII endonuclease site of cleavage present in the GnRH cDNA sequence spanned by the primers, yielding two digested products of the anticipated sizes (86 and 425 bp for the 511-bp fragment, and 86 and 311 bp for the 397-bp fragment). The complementary sequences for the GnRH probes were conserved in the 425-bp and 311-bp fragments. Based on these results, we can conclude that the RT-PCR products generated from RNA tissue were the target GnRH sequences in the anterior pituitary as well as in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Prolactin microadenoma in men. Study of 14 cases].

Macroprolactinomas have been well documented in men over the past several years. By contrast, to the best of our knowledge, there have been no reports of microprolactinomas in men. We describe here 14 cases of microprolactinomas occurring in male patients (14 to 53 years old) and discovered on the basis of endocrine symptoms. Nine patients complained of impotence and/or decreased libido, 8 had gynecomastia with or without galactorrhea, 1 had undergone incomplete puberty. All patients had hyperprolactinemia (225 +/- 65 micrograms/l, mean +/- SEM, N less than 13 micrograms/l); plasma testosterone levels were low in 9 (162 +/- 33 ng/dl, mean +/- SEM; N = 308 - 876 ng/dl), while plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and their responses to LH-releasing hormone (LHRH) were normal in all cases. Among the 14 patients, 12 had no hypopituitarism and 2 had only partial corticotrope insufficiency; none had visual disturbances and only one complained of headaches. The sella turcica was normal in size and shape in 2 cases but a double floor and/or a thinner part of the floor was observed in 12. CT scan of MRI demonstrated in all cases an intrasellar microadenoma with a mean size of 7 mm (range, 3 to 10 mm) and no preferential localization. One patient was treated with bromocriptine, while the others underwent surgery via the transsphenoidal route. Immunocytochemistry demonstrated immunoreactive-prolactin (IR-PRL) cells in all the adenomas. Surgery resulted in normalization of plasma PRL in 11 of the 13 patients and in lowering PRL levels in the others 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Neuropeptides of anterior pituitary origin. Autocrine or paracrine functions?

Several neuropeptides classically associated with the hypothalamus have been found in the anterior pituitary. The question arises whether they are locally synthesized and if they play a paracrine or autocrine role on pituitary cell functions. Using normal and tumoral human pituitaries we found neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries, while stimulatory hormones (TRH and GHRH) were predominantly found in tumoral tissue, implying an imbalance of pathophysiological importance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. The in situ synthesis was demonstrated for SRIH by the evidence of SRIH mRNA, the detection of SRIH immunoreactivity in peculiar cells and the presence of SRIH precursor. The possible role of these pituitary neuropeptides was suggested for instance by the negative correlation found in vitro between SRIH and GH secretions. Moreover, neuropeptides could interact with each other. Indeed DA stimulated TRH release while PRL secretion decrease at the same time. Pulses of TRH had differential effects on SRIH release according to the nature of the tissue as TRH inhibited SRIH release from adenoma while it stimulated SRIH release from normal pituitary. Concerning the effects of SRIH and GHRH on GH secretion, there was an endogenous regulatory pattern comparable to that observed in rat portal blood vessels. Pulses of GHRH induced GH secretion only when endogenous SRIH release was not stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1991

Apparently silent somatotroph adenomas.

We describe here 9 patients with somatotroph adenomas associated with mild features of acromegaly and basal plasma GH levels in the normal range. In 5 women and 4 men, 26 to 61 yrs old, the diagnosis of prolactinoma or non-secreting pituitary adenoma had been previously made on the basis of amenorrhea-galactorrhea or tumoral symptoms. However, they had discrete signs of coarsening of the facial features and moderate but evolutive changes of hand and foot sizes. Basal GH levels were in the normal range (0.4 to 4.5 micrograms/l, N less than 5 micrograms/l) but unaffected by oral glucose and insulin tolerance tests while IGF-I concentrations were elevated in all the cases (range 1.7 to 5.8 U/ml, N: 0.37-1.41 U/ml). Plasma PRL concentrations were elevated in 5 patients (range 16 to 80 micrograms/l, N less than 13 micrograms/l in men and N less than 19 micrograms/l in women). The 9 patients had a macroadenoma with an extrasellar extension in 8 of them and all were operated on by the transsphenoidal route. Immunocytochemical studies demonstrated IRGH-cells in all the adenomas and IRPRL-cells in 5 of them. Electron microscopic analysis of 3 tumors showed that the secretory granules were sparse and the Golgi apparatus poorly developed. Molecular biology of 7 tumors showed the presence of small amounts of GH mRNA. This result was in agreement with the morphological aspect, suggesting a low rate of GH synthesis. Thanks to these different approaches the diagnosis of silent somatotroph adenoma should sometimes be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1991

Pituitary enlargement with suprasellar extension in functional hyperprolactinemia due to lactotroph hyperplasia: a pseudotumoral disease.

Beside the well characterized PRL-secreting adenomas, a wide spectrum of functional hyperprolactinemic states exists. We describe here five women, 21-38 yr old, all suspected of having a PRL-secreting adenoma because of a pseudotumoral appearance of the pituitary on computerized tomographic (CT) scan or magnetic resonance imaging (MRI). Four had oligomenorrhea with or without galactorrhea, one had amenorrhea with galactorrhea, and two complained of infertility. In the same patient, basal plasma PRL levels were variable on different days, sometimes normal (mean +/- SEM, 11.3 +/- 1.5 micrograms/L), sometimes elevated (49 +/- 7 micrograms/L), but in all cases, a PRL response of large amplitude to TRH (6- to 8-fold increase in the basal value) was observed. Basal plasma levels of estradiol were within luteal phase normal values (0.41 +/- 0.13 pmol/L), while progesterone levels were low (1.92 +/- 0.47 nmol/L). CT scan or MRI showed an intrasellar mass with suprasellar extension, suggesting a tumoral process. However, the signal intensity was homogeneous, and on coronal views, the suprasellar extension was pyramidal and symmetrical, and the pituitary stalk was always in the midline. The five patients were operated on by the transsphenoidal route, but no adenoma was found. Surgical biopsies were taken in four cases, and lactotroph hyperplasia, i.e. enlarged cell cords consisting mainly of PRL cells, was found in three of them. One case displayed a continuum between areas of lactotroph hyperplasia and adenomatous PRL cells. We conclude that functional hyperprolactinemia may mimic on CT scan or MRI a PRL-secreting adenoma.

Adult↗

PubMed1991

[Presence and characterization of somatostatin precursor in human growth hormone secreting pituitary gland tumor].

Previous studies have demonstrated that normal and tumoral pituitaries release in vitro somatostatin (SRIH) and contain messenger RNAs encoding the preproSRIH. In the present study, we document the presence and characterization of the SRIH precursor in a growth hormone (GH)-secreting human pituitary adenoma, using two biochemical procedures: Sephadex G50 filtration and high performance liquid chromatography (HPLC). Sephadex G50 filtration of a 2M acetic acid extract demonstrated the presence of three SRIH-like immunoreactive (SLI) peaks, distinct from SRIH 1-28 and SRIH 1-14 used as standard. Molecular mass of the SLI material present in each peak was estimated as 21, 17 and 12 kilodaltons (kDa). SRIH 1-28 and/or 1-14 were not detected in this extract. Reverse phase HPLC was performed on a C18 column; all the three forms of SLI material coeluted with the rat hypothalamic proSRIH indicating a high homology between the human pituitary proSRIH and that of the rat hypothalamus. These results demonstrate for the first time the presence of high molecular mass proSRIH forms in a GH-secreting pituitary adenoma, and thus enable us to conclude for a local pituitary production of SRIH.

Chromatography, Gel↗

PubMed1990

Effect of oestradiol on dopamine receptors and protein kinase C activity in the rat pituitary: binding of oestradiol to pituitary membranes.

Oestradiol exerts an important modulatory influence on the release of prolactin which is accomplished partly through disruption of the inhibitory influence of dopamine. We have focused on the status of the anterior pituitary D2 dopamine receptor in female rats treated chronically with oestradiol or progesterone. A direct membrane effect of these steroids on the dopamine system was also investigated in vitro. Both steroids affected the status of the D2 receptor, oestradiol decreasing the number of sites in vitro and progesterone increasing it both in vitro and in vivo. The in vitro studies demonstrated that these steroids exert a direct membrane effect on the D2 receptor. These results correlated with an in vitro short-term physiological effect of oestradiol and progesterone on the dopaminergic inhibition of prolactin release, oestradiol decreasing it while progesterone had the opposite effect. Binding studies with [3H] oestradiol on pituitary membranes revealed a site for oestradiol of high affinity and low capacity, indicating that oestradiol's membrane effects could be mediated by a specific receptor. In vivo treatment with oestradiol also induces proliferation of prolactin-secreting cells (lactotrophs). We focused on the effect of oestradiol on protein kinase C activity, which is involved in both secretion and proliferation. In female rats treated with oestradiol total protein kinase C activity was increased by 74% (particulate 90%, soluble 71%) in comparison with controls. This effect was reversed by concomitant treatment with a dopamine agonist. Thus in the pituitary oestradiol and progesterone affect the characteristics of membrane components that are implicated in the physiological control of the cell. Whether these effects are post-transcriptional only or are also mediated through direct membrane mechanisms needs further investigation.

Animals↗