Biomedical subjects

F Peillon

Publications and source records attributed to F Peillon.

At least 55 records · Page 3Linked to original sources

PubMed1990

Changes of prolactin response to dopamine during the rat estrous cycle.

The effects of dopamine (DA) on prolactin (PRL) secretion in anterior pituitary tissue from rats selected during various stages of the estrous cycle were analyzed under in vitro conditions. The results were examined in relation to plasma PRL, estradiol and progesterone levels. During the estrous cycle there was a marked variation in the responsiveness of the lactotrophs to the inhibitory action of DA. Rapid changes occurred during proestrus: pituitary lactotrophs were not sensitive to the inhibitory action of 10 nM DA at 15.00 and 17.00 h and were less sensitive to 1 microM DA compared to 09.00 h (p less than 0.01), 12.00 h (p less than 0.05) and 19.00 h (p less than 0.05). This lowest PRL response to DA was associated with the preovulatory PRL surge. The recovery of a higher PRL response at 19.00 h coincided with the decrease of plasma PRL levels. During the remainder of the cycle, plasma PRL levels remained low in estrus, diestrus 1 and diestrus 2. Lactotrophs were sensitive to 1 microM and 10 nM DA during estrus and diestrus 2 but a significant lower PRL response to 1 microM DA (p less than 0.05) and no PRL response to 10 nM DA was observed in diestrus 1. These data show that alterations in the sensitivity of the lactotrophs' responsiveness to DA occur in the anterior pituitary gland during the rat estrous cycle and can lead to the removal of DA inhibition in the presence of physiological DA concentrations. This phenomenon is consistent with the fact that DA could be involved in the preovulatory PRL surge during the estrous cycle.

Animals↗

PubMed1990

Normal and adenomatous human pituitaries secrete thyrotropin-releasing hormone in vitro: modulation by dopamine, haloperidol, and somatostatin.

TRH is present in human normal pituitaries and in pituitary adenomas. In this study we demonstrated that the same tissues can release TRH in vitro. Fragments from seven normal pituitaries (10-15 mg/syringe) and dispersed cells from eight prolactinomas, four GH-secreting and two nonsecreting adenomas (1-3 x 10(6) cells/syringe) were perifused using a Krebs-Ringer culture medium. After 1 h of equilibration the perifusion medium was collected every 2 min (1 mL/fraction) for 3 h. TRH, PRL, and GH were measured by RIA under basal conditions and in the presence of 10(-10) to 10(-6) mol/L dopamine (DA), alone or concomitant with haloperidol, or in the presence of 10(-10) or 10(-6) mol/L somatostatin. Both normal pituitary fragments and pituitary adenomatous cells (from all types of adenomas studied) spontaneously released TRH in vitro. TRH was detected in the perifusion medium either immediately after the end of the equilibration period or 30-60 min later. The molecular identity of TRH was assessed by high pressure liquid chromatography. There was no difference in the profile and the rate of TRH secretion between normal and tumoral tissues, and no correlation was found between the level of TRH release and that of PRL or GH secretion. DA stimulated TRH release from normal pituitaries and from PRL- and GH-secreting adenomas at doses as low as 10(-10) mol/L. A concomitant decrease in PRL and GH release was observed from adenomatous cells and in one case of normal tissue. Haloperidol (10(-7) mol/L) antagonized the effect of 10(-8) mol/L DA on both TRH and PRL secretion in normal pituitary and in prolactinomas. DA had no effect on TRH release from two nonsecreting tumors. The amounts of TRH released during 1 h of perifusion were 60-1640 pg/2 mg wet wt tissue in normal pituitaries and 54-2174 pg/10(6) cells in adenomas; these values were very high compared to those precedently reported within the tissues. These results indicate that pituitary cells can release TRH in vitro and suggest that TRH might be synthesized in situ. We suggest that TRH could act on pituitary hormone secretion and/or cell proliferation via a paracrine and/or an autocrine mechanism.

Adenoma↗

PubMed1990

Chronic treatment by the calcium channel blocker +/- PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo.

In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with +/- PN 200-110 (3 mg.kg-1.day-1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 +/- 4.9 vs 95.0 +/- 9.1 micrograms/l, p less than 0.0001) and pituitary weight (19.9 +/- 0.4 vs 23.0 +/- 0.6 mg, p less than 0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Animals↗

PubMed1990

Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation.

Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level less than 4 micrograms/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 +/- 16.1 micrograms/l, mean +/- SEM). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1 +/- 0.37 vs 51.5 +/- 34.1 micrograms x (10(-6) cells) x min-1, p less than 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1990

[Neuropeptides of anterior pituitary origin].

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 hormone secretion. 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 on each other. Indeed DA stimulated TRH release while PRL secretion decreased 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 described in rat portal blood vessels. Pulses of GHRH induced GH secretion only when endogenous SRIH release was not stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Immunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome.

Four tumors consisting of pituitary adenomatous cells (AD) intricated with ganglion cells (GC) were studied. Each case was associated with a different clinical syndrome: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome with no hormonal hypersecretion. (a) In the case with acromegaly, immunoreactive growth hormone (IR-GH) was present in 80% of AD. IR-vasoactive intestinal peptide (VIP) was found in 5%-10% of AD and in few GC. Rare GC and processes showed IR-GH-releasing hormone (GRH), -somatostatin (SRIH), -gonadotropin-releasing hormone and -adrenocorticotropin-releasing hormone. (b) In the case with amenorrhea-galactorrhea, IR-prolactin (PRL) was seen in 90% of AD. IR-PRL and -VIP were present in rare GC. (c) In the case with Cushing's disease, 60% of AD and very few GC contained IR-adrenocorticotropin (ACTH) and beta-lipotropin. Rare GC processes contained IR-SRIH. (d) In the case without pituitary hormone hypersecretion, PRL was localized in rare AD and GC. Pituitary hormone and neuropeptides were never colocalized in the same cells. No case displayed IR-neurophysins or -thyroliberin. Pituitary hormones were localized by ultrastructural immunogold labeling. These findings show that: (i) in three cases, pituitary hormones (PRL and ACTH), and, in one case, VIP could be localized in both adenomatous and ganglion cells; (ii) the pituitary hormone-containing cells in the tumors could be related to the hypersecretory syndromes; (iii) intratumoral IR-VIP and -GRH might be involved in GH and PRL hypersecretion in the cases with acromegaly and amenorrhea-galactorrhea.

Acromegaly↗

PubMed1989

Receptors and neurohormones in human pituitary adenomas.

In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.

Adenoma↗

PubMed1989

Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone.

Neuropeptides such as vasoactive intestinal peptide, LHRH, or TRH have been found in rat pituitary tissue and could act via paracrine or autocrine actions in this tissue. In this study we investigated whether normal human pituitary tissue and GH-secreting human pituitary adenomas could release somatostatin (SRIH) and GHRH. Fragments from three human pituitaries and dispersed cells from six GH-secreting adenomas (four adenomas were studied for GHRH release and five for SRIH release) were perifused using a Krebs-Ringer culture medium, and the perifusion medium was collected every 2 min (1 mL/fraction for 5 h). GH, GHRH, and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L TRH or SRIH. Both normal pituitaries and GH-secreting pituitary adenomas released SRIH and GHRH. SRIH release commenced 90-180 min after initiation of the perifusion, at which time GH secretion had decreased significantly. TRH stimulated SRIH release from normal pituitary tissue and inhibited SRIH release from adenoma tissue. GHRH was present at the start of the perifusion, but rapidly disappeared. However, SRIH stimulated GHRH release from normal pituitary tissue, but not from adenoma tissue. Significant amounts of GHRH and SRIH were released during the experiments, suggesting their local synthesis. These results indicate that pituitary cells can release hypothalamic peptides. The liberation of these neuropeptides is regulated, and moreover, their regulation differs between normal and adenomatous pituitaries.

Adenoma↗

PubMed1989

Altered balance between thyrotropin-releasing hormone and dopamine in prolactinomas and other pituitary tumors compared to normal pituitaries.

We measured TRH and dopamine (DA) concentrations in prolactinomas and other pituitary tumors in order to further understand the roles of these two factors in the hormone hypersecretion and growth of these tumors. The mean TRH concentration (by RIA) in 16 prolactinomas was 247 +/- 92 (+/- SE) fmol/mg cell protein (range, 10-1297), near that found in normal pituitary tissue. The prolactinoma TRH content did not correlate with the patient's tumor size or plasma PRL level. By contrast, DA assayed by high pressure liquid chromatography was present in normal pituitary tissue (7.3 +/- 3.5 pmol/mg cell protein), but was very low or undetectable in the prolactinomas (23 fmol/mg cell protein or less). 3,4-Dihydroxyphenylacetic acid, also assayed by high pressure liquid chromatography, was undetectable in both normal pituitary tissue and prolactinomas. This imbalance between TRH and DA content also was found in GH-secreting and nonsecreting adenomas. The TRH content in 18 GH-secreting tumors (24 +/- 6 fmol/mg) was considerably lower than that in the prolactinomas (P less than 0.001). In 8 nonsecreting adenomas, the mean TRH concentration was 109 +/- 28 fmol/mg, about half of that in the prolactinomas. In those 2 types of adenomas, DA also was nearly undetectable (less than or equal to 73 fmol/mg cell protein). We conclude that the imbalance between TRH and DA contents in prolactinomas compared to those in normal pituitary tissue might participate in the mechanisms leading to hypersecretion of PRL and the growth of all types of pituitary adenomas.

Adenoma↗

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 of pre-prosomatostatin mRNA in human normal and tumoral anterior pituitary gland.

Expression of the SRIH gene was investigated in six human normal anterior pituitaries, six GH-, three PRL-, three mixed GH/PRL-secreting and four nonsecreting adenomas. Total cellular RNA and poly(A+) mRNAs were analyzed by dot and Northern blot hybridization to a 3'-end labeled oligonucleotide probe specific for the human pre-proSRIH mRNA. A weak but detectable pre-proSRIH hybridization signal was present in human normal anterior pituitaries and in the four groups of adenomas. The size of this pre-proSRIH mRNA was indistinguishable from that found in our hypothalamic samples and close to that described in the literature. The wide variation of the signal intensity from one case to the other in each group of the different types of normal and tumoral antehypophyseal samples prevented establishment of any correlation between the level of pre-proSRIH mRNA and the nature of the pituitary tissue. The presence of SRIH mRNA in human normal and tumoral anterior pituitary tissues provides a sound basis to substantiate the hypothesis of a SRIH biosynthesis in the human anterior pituitary gland.

Adenoma↗

PubMed1989

The stimulated C-kinase activity in estradiol-treated rat pituitaries is reduced by chronic treatment with the dopamine agonist CV 205-502.

To investigate whether the modulation of lactotrope cell multiplication and prolactin secretion in rat pituitary glands implicated the phosphoinositide C-kinase system, female Wistar rats were treated or not-with the dopamine agonist CV 205-502 or 8 days or with estradiol cervical implants for 8 for 15 days, alone or in combination with CV 205-502 for the last 8 days. CV 205-502 treatment induced a significant reduction in plasma PRL levels and in pituitary weights, whereas estradiol treatment induced a significant increase in both parameters. CV 205-502, in association with estradiol, counteracted estradiol stimulation of PRL levels and of pituitary weights. Total C-kinase activity in controls was 29.8 +/- 9.9 pmol 32phosphorus/min (N = 7, mean +/- SEM), mainly found in the soluble fraction (84%). When administered alone, CV 205-502 induced a significant reduction (-58%, p less than 0.02) in C-kinase activity in the particulate fraction with no modification in the soluble fraction. Both 8 and 15 days estradiol treatment induced a significant stimulation of total C-kinase activity, 74% and 155% respectively. When combined with estradiol, CV 205-502 significantly (p less than 0.02) counteracted the estradiol increase in total C-kinase activity, which was only 45% over control values. We conclude that treatment with a dopamine agonist and estradiol, which have antagonistic effects on the pituitary, exerts an opposite regulation of C-kinase activity. Whether this may be one of the mechanisms involved in their interaction on pituitary lactotropes remains to be determined.

1-Phosphatidylinositol 4-Kinase↗

PubMed1989

[Neurohormones coming from the normal and tumoral human anterior pituitary. Secretion and regulation in vitro].

Several neuropeptides, classically associated with the hypothalamus have been found in the anterior pituitary and their local synthesis has been hypothesized. Using normal and tumoral human pituitaries we found in the tissue itself different neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries while only stimulatory neurohormones like TRH and GHRH were found in tumoral tissue implying an imbalance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Fragments from normal pituitaries and dispersed cells from GH, PRL and nonsecreting adenomas, were perifused for 4 hours in a Krebs-Ringer medium collected every 2 min and GH, PRL, TRH, GHRH and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L DA, TRH or SRIH. Neuropeptides and DA were characterized by HPLC. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. There was an in situ regulation between SRIH and GH as their secretion profile was negatively correlated, GH secretion decreasing while SRIH secretion was increasing. Moreover the release of TRH was stimulated 5 to 20 folds by DA, while PRL decreased at the same time. Pulses of TRH and SRIH had differential effects on GHRH and SRIH release according to the nature of the tissue as TRH stimulated SRIH release from normal pituitary while it inhibited SRIH release from adenoma. These results indicate that anterior pituitary cells can release neuropeptides which are probably endogenously synthesized and have a local regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1988

Absence of receptors for thyrotropin (TSH)-releasing hormone in human TSH-secreting pituitary adenomas associated with hyperthyroidism.

In patients with TSH-secreting pituitary adenomas associated with hyperthyroidism, TSH secretion usually does not respond to exogenous TRH stimulation. To determine the basis for this unresponsiveness, we studied TRH binding to the membranes of two such TSH-secreting pituitary adenomas. The patients, a 28-yr-old man and a 60-yr-old woman, had clinical and biochemical hyperthyroidism with increased serum TSH levels (15.7 and 14 mU/L, respectively; normal range, 1.1-7.2) and alpha-subunit to TSH molar ratios greater than 1 (2.4 and 1.7, respectively). Neither patients had an increase in serum TSH in response to TRH (200 micrograms, iv). Immunocytochemistry of the two adenomas, removed by transsphenoidal surgery showed a pure population of thyrotropic cells. Binding studies were performed by incubation of tumor cell membrane suspensions with increasing amounts of [3H]TRH. Two PRL-secreting adenomas and one normal human pituitary were used as controls. The characteristics of the TRH-binding sites from the control tissues were similar to those previously reported (Kd, 56, 30, and 49 nM; maximum binding, 187, 46, and 94 fmol/mg protein, respectively). In contrast, no specific TRH binding was found in the two TSH-secreting adenomas. We conclude that the unresponsiveness of TSH after TRH administration is related to the absence of specific TRH-binding sites in these thyrotropic tumors.

Adenoma↗

PubMed1988

[In vitro secretion of somatostatin (SRIH) by human adenomatous somatotropic cells. Relation with somatotropic hormone (GH) release and modulation by thyroliberin (TRH)].

SRIH and GH secretions by GH-secreting adenomatous human pituitary cells were analyzed in vitro in a perifusion system. Of the 13 adenomas studied, 7 secreted SRIH, in variable amounts (50 to 700 pg/ml/2 min., corresponding to 600 10,700 pg for the total experiment. SRIH secretion increased during the perifusion, the highest levels being observed at the end of the perifusion. GH secretion also varied from one adenoma to the other (6 to 500 ng/ml). In most cases, the secretion profiles were negatively correlated, GH secretion decreasing while SRIH secretion was increasing. In the presence of 10(-7) M TRH, GH secretion increased while that of SRIH decreased. The hypothesis of a paracrine and/or an autocrine role for SRIH as well as its possible in situ synthesis are discussed.

Adenoma↗

PubMed1988

[Release of thyrotropin releasing hormone (TRH) from human prolactin-secreting pituitary adenoma cells. Modulation by dopamine].

We found, by radioimmunoassay, that thyrotropin-releasing-hormone (TRH) was present in human prolactin (PRL)-secreting adenomas (mean: 89 +/- 45 (SEM) fmol/mg proteins) and was released by perifused adenomatous cells at levels varying from 5 to 60 fmol/10(6) cell/2 min. TRH release was increased in the presence of dopamine (DA) 10(-6) M but was not modified by the presence of somatostatin (SRIH) 10(-6) M.

Adenoma↗

PubMed1987

Binding of (+)-PN 200-110 to rat pituitaries and to normal and adenomatous human pituitaries.

Endocrine cells possess voltage-sensitive Ca2+ channels involved in the modulation of hormonal secretion. Using the dihydropyridine, (+)-PN 200-110, we have investigated the binding characteristics of this ligand to pituitary membrane Ca2+ channels from normal rat, normal and adenomatous human pituitaries. [3H]PN 200-110 binds specifically to rat pituitary membranes to one class of sites (Kd = 0.41 +/- 0.10 mM; Bmax = 39 +/- 1.3 fmol/mg protein). At 37 degrees C, equilibrium is reached in 45 min and half-life of the binding is 13 min. No significant changes were observed for either the Kd or Bmax values between normal rat and human pituitaries or between the different types of adenomas (GH- and PRL-secreting and non-secreting). As the secretory activity of the pituitary adenomas, involving Ca2+ mobilization, varies from one adenoma to another, our results could indicate that, if there is a modified regulation of Ca2+ entry in the adenomas, it may not be related to a varying number of calcium channels, at least the channels labeled by the dihydropyridine (+)-PN 200-110.

Adenoma↗

PubMed1987

Epidermal growth factor-binding sites, present in normal human and rat pituitaries, are absent in human pituitary adenomas.

To investigate the involvement of epidermal growth factor (EGF) and its receptor in the pathogenesis of human pituitary adenomas, we examined the presence of EGF-binding sites in normal rat and human pituitaries and in human PRL- and GH-secreting and nonsecreting pituitary adenomas. Using crude membrane preparations, specific binding for [125I] EGF was found in normal rat and human pituitaries. Equilibrium was reached at 25 C in 40 min. There was no change in the Kd values between male rats [Kd, 0.65 +/- 0.35 nM (mean +/- SD)] and female rats (Kd, 0.51 +/- 0.15 nM), while the maximum capacity was significantly higher (P less than 0.05) in male rats (21 +/- 8 fmol/mg protein) than in female rats (10 +/- 2 fmol/mg protein). Scatchard analysis of the data suggested the presence of a single class of binding sites. In the three normal human pituitaries tested, specific [125I]EGF binding was also demonstrated. However, both the Kd and the maximum capacity varied widely. Twenty-two human pituitary adenomas were tested, but no specific binding was detected in any of them. In addition to the binding experiments, a radioreceptor assay using rat liver membranes was developed to detect EGF or EGF-like material in extracts of six human pituitary adenomas (two of each type). No EGF activity was detected in any of the extracts. From these results, we conclude that EGF-binding sites are present in normal pituitary tissue, suggesting a physiological role for EGF in this tissue. Consequently, the reason(s) for the lack of EGF binding in pituitary adenoma membranes is not known.

Adenoma↗