Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SECRETION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

Quantitative studies of prostatic secretion. III. Simultaneous measurement of size and secretion of the canine prostate and the interaction of androgenic and estrogenic substances thereon.

The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion. Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them. When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered. Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined. The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase content of the prostatic secretion in the regions of secretory plateaus was similar to that of castrate dogs injected with androgen alone. The plateau phenomenon is due to simultaneous physiologic action of androgenic and estrogenic compounds on the prostatic cells. The depression of prostatic secretion resulting in the plateau phenomenon is due to both functional and structural changes in the prostatic epithelium. They are best explained on the assumption that differences in steroid threshold exist in groups of cells within the prostate, those of the anterior rim of the gland being least susceptible to estrogenic activity.

Androgens↗

Dietary fish oil increases tumor necrosis factor secretion but decreases interleukin-10 secretion by murine peritoneal macrophages.

Dietary fish oil has immunomodulatory effects that are mediated in part by its effects on cytokines. Secretion of the inflammatory and the anti-inflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-10 by murine resident peritoneal macrophages was monitored after ex vivo stimulation with lipopolysaccharide. Macrophages were obtained from mice fed a corn oil diet containing 200 g/kg corn oil or a fish oil diet containing 180 g/kg fish oil and 20 g/kg corn oil. Dietary fish oil increased secretion of the proinflammatory cytokine, TNF, but decreased secretion of the anti-inflammatory cytokine, IL-10. The cytokines appeared in the medium after 1.5 h and peaked at 6-12 h. Neutralizing antibodies against TNF and IL-10 had little effect on secretion of the other cytokine, indicating that the effects of fish oil on TNF and IL-10 secretion by these cells are independent of one another. Furthermore, although inhibiting prostaglandin production enhanced TNF secretion by macrophages from mice fed the corn oil diet, it did not affect IL-10 secretion by macrophages in this group. Blocking leukotriene B(4) production also did not affect IL-10 secretion in macrophages from mice fed a nonpurified diet. These results demonstrate that fish oil has an overall pro-inflammatory effect given its effects on secretion of both inflammatory and anti-inflammatory cytokines by resident peritoneal macrophages.

Animals↗

Secretion of YscP from Yersinia enterocolitica is essential to control the length of the injectisome needle but not to change the type III secretion substrate specificity.

The length of the needle of the Yersinia Ysc injectisome is determined by a protein called YscP. This protein, which acts both as a molecular ruler and as a substrate-specificity switch for type III secretion is itself secreted by the injectisome. In this report, we address the question why YscP is secreted. By a systematic deletion analysis and by fusing different parts of the molecule to the adenylate cyclase reporter, we identified two independent secretion signals. One of them is encompassed within the 35 N-terminal residues while the second one spans residues 97-137. These two signals are functionally different from Yop secretion signals. When both secretion signals were removed, Yops could still be secreted but the needle length control was lost. YscP possessing only one signal did not control needle length properly but the control was improved when more YscP was produced and secreted. YscP deprived of both signals could not control length, even when overproduced. We conclude from this that YscP needs to be secreted to exert its length control function but not its substrate-specificity switch function.

Bacterial Proteins↗

Structure of yeast pGKL 128-kDa killer-toxin secretion signal sequence. Processing of the 128-kDa killer-toxin-secretion-signal-alpha-amylase fusion protein.

The linear double-stranded DNA plasmid pGKL1 in yeast encodes a killer toxin consisting of 97-kDa, 31-kDa and 28-kDa subunits. A 128-kDa protein precursor of the 97-kDa and 31-kDa subunits, was first synthesized with a 29-amino-acid extension at its NH2-terminus as a secretion signal sequence. In the present study, the property of this signal sequence was studied by the analysis of a fusion protein with mouse alpha-amylase. Using the secretion signal sequence of the killer protein, the mouse alpha-amylase was successfully secreted into the culture medium. An intracellular precursor form of alpha-amylase was identified and purified. Analysis of the NH2-terminal sequence of this precursor molecule indicated that it corresponded to the secretory intermediate (pro form) of alpha-amylase with the removal of the hydrophobic segment (Met1-Gly16) of the secretion signal. Both the secretion of alpha-amylase into the culture medium and the detection of the pro-alpha-amylase species in the cells were prohibited by a sec 11 mutation, or by the conversion of Gly to Val at the 16th position of the secretion signal. These results strongly suggest that the cleavage occurs between Gly16 and Leu17 by a signal peptidase, and that this cleavage is required for the secretion of alpha-amylase into the medium. Based on the data from the NH2-terminal amino acid sequences of secreted alpha-amylases, we conclude that the 29-amino-acid secretion signal present in the 128-kDa killer toxin precursor protein is a prepro structure.

Amino Acid Sequence↗

Influences of the sympatho-adrenal system on gastric motility and acid secretion and on gastroduodenal bicarbonate secretion in the cat.

Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. Gastric H+ and HCO3- secretions were calculated from the pH and PCO2 in a luminal perfusate. Gastric motility was reflected by changes in hydrostatic pressure within the luminal perfusion system ('intragastric pressure'). Duodenal HCO3- secretion was monitored by pH titration in situ. Animals with an intact sympatho-adrenal system (group 1) were compared with others subjected to splanchnicotomy (group 2), adrenal gland ligation (group 3), and splanchnicotomy plus adrenal gland ligation (group 4). Basal gastric H+ secretion, as well as vagally induced H+ secretory responses, did not differ significantly between groups. Basal gastric HCO3- secretion was lower in all groups with a manipulated sympatho-adrenal system compared to the intact controls. Vagally induced increases in gastric HCO3- secretion were enhanced in the splanchnicotomized groups (groups 2 and 4). Basal as well as vagally induced increases in intragastric pressure and duodenal HCO3- secretion were enhanced in animals subjected to splanchnicotomy, with or without simultaneous adrenal gland ligation (groups 2 and 4). Adrenal gland ligation per se had no such effects. The results suggest that the adrenal glands exert a stimulatory action on basal gastric HCO3- secretion. Basal intragastric pressure and basal duodenal HCO3- secretion are inhibited by post-ganglionic sympathetic neurons, not involving the adrenal glands. Also, vagal excitatory effects on gastric motility, as well as on gastric and duodenal HCO3- secretions, are inhibited by such a direct neural mechanism.

Adrenal Glands↗

Mutations in HlyD, part of the type 1 translocator for hemolysin secretion, affect the folding of the secreted toxin.

HlyD, a member of the membrane fusion protein family, is essential for the secretion of the RTX hemolytic toxin HlyA from Escherichia coli. Random point mutations affecting HlyA secretion were obtained, distributed in most periplasmic regions of the HlyD molecule. Analysis of the secretion phenotypes of different mutants allowed the identification of regions in HlyD involved in different steps of HlyA translocation. Four mutants, V349-I, T85-I, V334-I and L165-Q, were conditionally defective, a phenotype shown to be linked to the presence of inhibitory concentrations of Ca2+ in extracellular medium. Hly mutant T85-I was defective at an early stage in secretion, while mutants V334-I and L165-Q appeared to accumulate HlyA in the cell envelope, indicating a block at an intermediate step. Mutants V349-I, V334-I, and L165-Q were only partially defective in secretion, allowing significant levels of HlyA to be transported, but in the case of V349-I and L165-Q the HlyA molecules secreted showed greatly reduced hemolytic activity. Hemolysin molecules secreted from V349-I and V334-I are defective in normal folding and can be reactivated in vitro to the same levels as HlyA secreted from the wild-type translocator. Both V349-I and V334-I mutations mapped to the C-terminal lipoyl repeat motif, involved in the switching from the helical hairpin to the extended form of HlyD during assembly of the functional transport channel. These results suggest that HlyD is an integral component of the transport pathway, whose integrity is essential for the final folding of secreted HlyA into its active form.

Amino Acid Motifs↗

Molecular basis for defective secretion of the Z variant of human alpha-1-proteinase inhibitor: secretion of variants having altered potential for salt bridge formation between amino acids 290 and 342.

Human alpha-1-proteinase inhibitor (A1PI) deficiency, associated with the Z-variant A1PI (A1PI/Z) gene, results from defective secretion of the inhibitor from the liver. The A1PI/Z gene exhibits two point mutations which specify amino acid substitutions, Val-213 to Ala and Glu-342 to Lys. The functional importance of these substitutions in A1PI deficiency was investigated by studying the secretion of A1PI synthesized in COS cells transfected with A1PI genes altered by site-directed mutagenesis. This model system correctly duplicates the secretion defect seen in individuals homozygous for the A1PI/Z allele and shows that the substitution of Lys for Glu-342 alone causes defective secretion of A1PI. The substitution of Lys for Glu-342 eliminates the possibility for a salt bridge between residues 342 and 290, which may decrease the conformational stability of the molecule and thus account for the secretion defect. However, when we removed the potential to form a salt bridge from the wild-type inhibitor by changing Lys-290 to Glu (A1PI/SB-290Glu), secretion was not reduced to the 19% of normal level seen for A1PI/Z-342Lys; in fact, 75% of normal secretion was observed. When the potential for salt bridge formation was returned to A1PI/Z-342Lys by changing Lys-290 to Glu, only 46% of normal secretion was seen. These data indicate that the amino acid substitution at position 342, rather than the potential to form the 290-342 salt bridge, is the critical alteration leading to the defect in A1PI secretion.

Amino Acid Sequence↗

Effects of eight weeks' continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin.

Gastric acid secretion, pepsin secretion, and fasting serum gastrin levels were measured in 23 patients with duodenal ulcer disease, divided into three groups which received either cimetidine 800 mg daily, cimetidine 1600 mg daily, or ranitidine hydrochloride 300 mg daily for eight weeks. Pentagastrin tests were carried out at intervals both before and after treatment. Each dose of cimetidine reduced acid secretion to 42% of control one week after starting therapy. Ranitidine reduced acid secretion to 33% of the pretreatment value. Acid secretion remained suppressed to these levels throughout treatment with each drug. Acid secretion returned to pretreatment levels in all patients one week after treatment and remained normal until the end of the study. Both drugs reduced pepsin, which fell to 64% and 61% (p less than 0.01) after 800 mg and 1600 mg cimetidine respectively and to 65% (p less than 0.005) with ranitidine after one week's treatment. Pepsin secretion remained at this reduced level in both cimetidine groups till the end of treatment. Pepsin levels fell to 50% at two weeks of therapy with ranitidine but stabilised at this level till the end of therapy. Cimetidine withdrawal was followed by a return towards pretreatment levels of pepsin secretion; but secretion remained significantly depressed (p less than 0.05) to the end of the study period. In the ranitidine-treated patients pepsin output returned to normal after drug withdrawal. Fasting gastrin levels rose during treatment with both drugs but failed to reach significant levels. After withdrawal of treatment fasting serum gastrin levels returned to normal in all three groups of patients.

Anti-Ulcer Agents↗

Gastric inhibitory polypeptide and glucagon-like peptide-1(7-36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach.

Previous studies on the isolated perfused stomach have shown that gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1(7-36) amide) stimulate release of somatostatin (somatostatin-like immunoreactivity, SLI). GIP produced a paradoxical increase in gastrin secretion, whereas GLP-1(7-36) was inhibitory. In the current study, the actions of synthetic (sp) and native (np) porcine and synthetic human (sh) GIP, GLP-1(7-36), and GLP-1(7-37) on SLI and gastrin secretion were compared using a gradient perfusion of peptide. All peptides increased SLI secretion at a threshold concentration of approximately 50 pmol/L (p < 0.05). The initial rate of increase in response to spGIP (119 +/- 39 pg/min) was greater than with other forms of GIP or GLP-1. Maximal increases obtained with the two porcine peptides did not differ. Gastrin secretion was increased by concentrations of spGIP and npGIP similar to those increasing SLI secretion, but the maximal response to shGIP was lower. In contrast to GIP-induced increases, both GLP-1(7-36) and GLP-1(7-37) suppressed gastrin secretion. It is concluded that human and porcine GIP, GLP-1(7-36), and GLP-1(7-37) all stimulate SLI secretion but with different maximal effects, and GIP stimulates gastrin secretion whereas both forms of GLP-1 inhibit gastrin secretion.

Animals↗

Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly.

Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretion.

Acromegaly↗

Anion secretion drives fluid secretion by monolayers of cultured human polycystic cells.

We have investigated the hypothesis that active anion transport drives fluid secretion by the cystic epithelium in autosomal dominant polycystic kidney disease (ADPKD). We prepared monolayers of a primary culture derived from cystic tissue removed from ADPKD patients. The monolayers were grown on permeant supports, and fluid secretion was initiated by forskolin. The results were compared with those obtained with monolayers of Madin-Darby canine kidney (MDCK) cells, known to secrete Cl-. In the absence of the agonist, ADPKD monolayers absorbed fluid (0.20 +/- 0.02 microliter.cm surface area-2.h-1). Forskolin reversed this to secretion (0.60 +/- 0.03 microliter.cm-2.h-1). Control MDCK monolayers did not transport fluid in either direction, but forskolin induced secretion (0.48 +/- 0.03 microliter.cm-2.h-1). The electrical properties of the monolayers were monitored in Ussing chambers. Forskolin increased the transepithelial potential difference (Vte) of ADPKD monolayers (-0.9 +/- 0.1 to -1.1 +/- 0.1 mV) and the short-circuit current (Isc) (6.6 +/- 0.7 to 9.2 +/- 0.8 microA/cm2). The transepithelial resistance (Rte) fell (156 +/- 9 to 138 +/- 10 omega.cm2). Similar results were obtained with MDCK monolayers. The polarity of Vte and the direction of the Isc are compatible with the hypothesis that active secretion of anion drives fluid secretion. Basolateral application of the Na-K-2Cl cotransporter, bumetanide, reduced forskolin-stimulated fluid secretion by ADPKD monolayers (0.56 +/- 0.05 to 0.28 +/- 0.03), depolarized Vte, and inhibited Isc without affecting Rte. Apical application of the Cl- channel blocker, diphenylamine-2-carboxylate, also inhibited fluid secretion by ADPKD monolayers (0.65 +/- 0.03 to 0.27 +/- 0.02 microliter.cm-2.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells: identification of fibronectin in the differential secretion proteome.

The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FCHL) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or normolipidemic controls. Overall protein secretion was 10-15% higher after incubation with FCHL plasma. This was specifically caused by an increase in four secreted proteins, with estimated sizes of 240, 180, 120, and <40 kD (P < 0.001, P < 0.006, P < 0.002, P < 0.02, respectively). The 240 kD protein in the secretion proteome was identified as fibronectin by mass spectrometry. Plasma fibronectin concentrations were elevated in FCHL patients, confirming biological relevance of these data. Overall protein secretion by HepG2 cells correlated with concentrations of triglycerides (r = 0.61, P < 0.001) in the applied plasma samples. VLDL+IDL isolated from FCHL patients, induced a higher protein secretion than lipoproteins isolated from controls (P < 0.001). Remarkably, secretion of apoB, the structural protein of VLDL, was stimulated to a similar extent by FCHL and control plasma. FCHL plasma did not induce excess secretion of apoB by HepG2 cells compared with control plasma. FCHL plasma did stimulate secretion of several distinct hepatic proteins, among which fibronectin was identified.

Apolipoproteins B↗

Antithyrotropin-releasing hormone serum inhibits secretion of glucagon from isolated perfused rat pancreas: an experimental model for positive feedback regulation of glucagon secretion.

TRH is synthesized in the islets of Langerhans and was found in the perfusate of isolated rat pancreas. In the present study, designed to determine the role of endogenous TRH, we first characterized chromatographically the identity of immunoreactive TRH with synthetic pGlu-His-Pro-NH2. Since endogenous TRH secretion may mask the effects of exogenous TRH, we performed, in parallel to dose-response studies, immunoneutralization experiments using anti-TRH serum to neutralize the endogenous TRH secretion from isolated perfused rat pancreas. The data indicate that exogenous TRH enhances basal glucagon secretion; inversely, anti-TRH serum inhibits glucose plus arginine-induced glucagon secretion and produces a concomitant slight inhibition of somatostatin secretion. The present study shows a physiological contribution for endogenous TRH as a local modulator of intraislet hormone regulation; from these observations, we postulate a direct effect of pancreatic TRH on glucagon-containing (alpha) cell secretion, which, in turn, may produce the fluctuation in somatostatin secretion. Local TRH secretion provides a model for positive feedback regulation of glucagon secretion, frequently associated with diabetes.

Animals↗

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion.

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.

Animal Feed↗

Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH, and PRL secretion.

Somatostatin (SRIF) analogs interacting with SRIF receptor subtype (SSTR) 2 and SSTR5 are known to reduce secretion in GH-secreting pituitary adenomas. We investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH and prolactin (PRL) secretion and cell viability in primary cultures deriving from 15 GH- and PRL-secreting adenomas expressing SSTR1. Quantitative RT-PCR showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/ microg reverse-transcribed total RNA. SSTR2 and SSTR5 were frequently expressed (93.3%), on the contrary of SSTR3 (53.3%) and SSTR4 (6.7%). GH secretion was significantly reduced by SRIF and BIM-23926 (45 +/- 8.6% and 32 +/- 18.1% inhibition, respectively) as well as PRL secretion (16.1 +/- 4% and 19.7 +/- 3.5% inhibition, respectively). After treatment with SRIF and BIM-23926, cell viability was significantly reduced by 17.5 +/- 5% and 20 +/- 3.9%, respectively. SSTR1 mRNA levels correlated with the degree of GH and PRL secretion inhibition. These results demonstrate that SSTR1 selective activation inhibits hormone secretion and cell viability in GH- and PRL-secreting adenomas in vitro and suggest that SRIF analogs with affinity for SSTR1 may be useful to control hormone hypersecretion and reduce neoplastic growth of pituitary adenomas.

Adenoma↗

Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison with the inhibitory effects of octreotide upon in vivo and in vitro hormonal secretions.

The in vivo and in vitro inhibitory effects of a somatostatin (SRIH) analog, octreotide, upon TSH, alpha-subunit, GH, and PRL have been studied, as well as SRIH receptors and their coupling to adenylate cyclase, in nine TSH-secreting pituitary adenomas. From in vivo and cell culture studies, the TSH- and alpha-subunit-secreting adenomas appeared heterogeneous, with four out of the nine tumors cosecreting GH and/or PRL. A single sc injection of octreotide (100 micrograms) lowered plasma concentration of TSH by 40 +/- 5% (mean +/- SE of 5), of alpha-subunit by 27 +/- 9% (n = 5), of GH by 60 +/- 5% (n = 4), and of PRL by 27 +/- 9% (n = 4). In cells cultures, octreotide (10(-8) mol/L) inhibited equally TSH, alpha-subunit, and GH release. 125I-Tyr0-DTrp8-SRIH binding sites were measurable in the nine TSH-secreting adenomas either on membrane preparations (n = 6; Bmax: 152 +/- 73 fmol/mg protein) or on frozen sections by radioautography (n = 3). Their density was variable among TSH adenomas and was lower than that measured in GH-secreting adenomas but higher than in nonfunctioning tumors. Two out of three TSH-secreting adenoma displayed an heterogeneous distribution of 125I-Tyr0-DTrp8-SRIH binding sites. 125I-Tyr0-DTrp8-SRIH specific binding was inhibited by guanosine triphosphate (GTP: 10(-4) mol/L). SRIH inhibited adenylate cyclase in 5/5 TSH-secreting adenomas and a good correlation (r = 0.92, P less than 0.02) was found between 125I-Tyr0-DTrp8-SRIH binding capacity (Bmax) and maximal adenylate cyclase inhibition by SRIH. These results demonstrate in vivo and in vitro inhibition of TSH, alpha-subunit, PRL, and GH secretion by octreotide in TSH-secreting pituitary adenomas. Functional SRIH receptors are present on these tumors and the effect of SRIH on hormonal secretion could be mediated, at least in part, by inhibition of adenylate cyclase. These findings support the medical treatment of this rare type of tumors by SRIH analogs.

Adenoma↗

[Effects of 1,25-(OH)2D3 on the secretion of growth hormone by human pituitary growth hormone-secreting tumors in vitro].

This work studied the effects of 1,25-(OH)2D3 on the secretion of growth hormone (GH) in 15 cases of human pituitary GH-secreting tumor cell cultures. At physiological doses (40-80 pg/ml) of 1,25-(OH)2D3, a GH secretion response was found in 14 cases of pituitary tumor: GH secretion was suppressed significantly in 9 of 14 cases and was markedly stimulated in only 2 of 14 cases of pituitary tumors. In the other 3 cases, the GH response was variable at different days of culture. The degree of suppression of GH secretion induced by 1,25-(OH)2D3 in all cases was 63.1 +/- 3.3% (means +/- sx of the control, and the average increase of GH secretion was 164.0 +/- 6.2% of control. There was no correlation between the type of GH reaction and the dose rang of 1,25-(OH)2D3 used in the experiment. The stimulatory effect on GH secretion did not appear after 2 weeks of culture. The results demonstrate that 1,25-(OH)2D3 at physiological doses has a direct regulatory effect (mainly suppressive) on GH secretion in most pituitary GH-secreting tumors in cell culture.

Adenoma, Acidophil↗

Subpopulations of Ig-secreting cells induced by peroxidase immunization: discrimination according to antibody storage and secretion.

Mice were injected in their hind footpads with peroxidase (PO) emulsified in Freund's complete adjuvant. The development of cells secreting anti-peroxidase antibody (Ab) and cells secreting immunoglobulins (Ig) were detected in the draining popliteal lymph nodes in the subsequent 35 days, using local haemolysis plaque assay with sheep red cell blood cells coated with either PO or anti-mouse Ig antibody. Plaque-forming cells (PFC) were isolated from the centre of plaques by micromanipulation and after appropriate treatment, were examined by electron microscopy for their intracellular Ab content and in corporation of [3H]-thymidine. Four subpopulations of Ig secreting cells were distinguished: (1) cells secreting Ig without Ab function and not containing intracellular Ab detectable between days 5 and 20; (2) cells secreting Ig without Ab function but containing Ab appearing on day 6 and present throughout the immune response; (3) cells secreting Ab and containing Ab; (4) cells secreting Ab, but without detectable intracellular Ab. These last subpopulations appeared on day 7 and were found in all subsequent assays. The analysis of the kinetics of these subpopulations suggest that cells secreting Ig without Ab function might be precursors of Ab secreting cells.

Animals↗