Biomedical subjects

S Melmed

Publications and source records attributed to S Melmed.

At least 181 records · Page 10Linked to original sources

PubMed1987

Cushing's syndrome due to ectopic proopiomelanocortin gene expression by islet cell carcinoma of the pancreas.

Expression of proopiomelanocortin (POMC) was studied in a male patient with Cushing's syndrome and ectopic production of ACTH by a pancreatic carcinoma. Plasma ACTH levels (greater than 200 pg/ml) were elevated, and elevated serum cortisol and urinary free cortisol were partially suppressed to 25% of basal levels by high-dose dexamethasone. Petrosal and jugular vein sampling did not yield a gradient of ACTH. Immunohistochemical staining of tumor tissue removed at pancreatectomy was positive for ACTH and beta endorphin, and negative for corticotropin-releasing factor (CRF). Tumor cells cultured in vitro secreted ACTH and beta-endorphin, which comigrated with their respective radiolabeled standards on gel chromatography. Hydrocortisone suppressed in vitro ACTH secretion and CRF (100 nM) stimulated ACTH by 50% during 72 hours of incubation. Agarose gel electrophoresis of poly-(A) mRNA extracts of tumor tissue followed by hybridization with 32P-cDNA for POMC revealed 2 distinct RNA species. The major RNA species (about 1.0 kb) was smaller than authentic pituitary POMC mRNA (about 1.1 kb); a larger precursor band also was visualized, suggesting either processing or degradation of tumor-POMC mRNA. Cytoplasmic dot blot hybridization of tumor mRNA with POMC cDNA yielded a positive signal with increasing amounts of RNA blotted. Immunohistochemistry and radioimmunoassay (RIA) of ACTH, in vitro regulation of ACTH secretion, and expression of POMC mRNA species by this tumor document expression of the human POMC gene by an islet carcinoma associated with Cushing's syndrome.

Adenoma, Islet Cell↗

PubMed1987

Suppressed serum prolactin in sinoaortic-denervated rats.

We investigated the effect of arterial baroreceptor deafferentation on serum and pituitary prolactin (PRL) and on catecholamines in median eminence (ME) and anterior and posterior pituitaries. Male Wistar rats were sinoaortic denervated (SAD) or sham operated (SO). Three days after surgery serum prolactin, measured by radioimmunoassay, was suppressed in SAD rats (-54%, P less than 0.05), and dopamine (DA) and norepinephrine (NE) concentrations, measured by radioenzymatic or high-performance liquid chromatography electron capture methods, were significantly reduced in ME of SAD rats (NE, -54% P less than 0.005 and DA, -56% P less than 0.001). Simultaneously, anterior pituitary of SAD rats had significant increases in both catecholamines, whereas posterior pituitary showed no changes. Four hours after surgery serum PRL was also reduced (-40%, P less than 0.05) in SAD rats, but no changes in ME catecholamines were found. Mean arterial pressure (MAP) and heart rate were measured before and after injection of bromocriptine (0.5 mg/kg ip) in SAD and SO rats 3 days after surgery. Bromocriptine markedly suppressed serum PRL in both groups and reduced MAP from 144 +/- 10 to 84 +/- 5 and from 116 +/- 2 to 99 +/- 3 in SAD and SO rats, respectively; heart rate was reduced in SAD rats. We conclude that the SAD rat is a model of hypertension with suppressed serum PRL and that interruption of arterial baroreceptor nerves suppresses PRL secretion probably by modulating tuberoinfundibular turnover of catecholamines.

Animals↗

PubMed1987

Insulinlike growth factor I regulation of growth hormone gene transcription in primary rat pituitary cells.

We have previously shown that insulinlike growth factor I (IGF-I) inhibits growth hormone (GH) secretion and messenger RNA (mRNA) levels in pituitary cells. The effects of IGF-I on new GH mRNA synthesis rates in primary monolayer rat pituitary cells were therefore examined by nuclear runoff transcription assays. IGF-I (1.3 nM) treatment for 1 h inhibited GH gene transcription to 60% of controls. IGF-I (3.25 nM) maximally suppressed GH gene transcription to 30% of control values after 4 h. After 24 h treatment, GH transcription was suppressed to 48% of controls by 3.25 nM IGF-I. IGF-I (3.25 nM) also inhibited the twofold growth hormone-releasing hormone (GHRH) (10 nM)-stimulated GH gene transcription by 30% after 4 h. Transcription of the prolactin (PRL) gene was not suppressed in these cells by IGF-I. Relatively high doses of insulin (200 nM) also suppressed GH gene transcription, but epidermal growth factor and fibroblast growth factor did not change GH mRNA synthesis. The results show that IGF-I exerts a rapid and selective suppression of basal and GHRH-stimulated GH gene transcription. These data indicate a role for IGF-I in negative feedback of GH gene expression and provide evidence for the direct transcriptional regulation of the GH gene by IGF-I in primary rat anterior pituitary cells.

Animals↗

PubMed1987

Insulin-like growth factor I induces c-fos messenger ribonucleic acid in L6 rat skeletal muscle cells.

Insulin-like growth factor I (IGF-I) mediates growth promotion of GH on specific target cells. As other growth factor action has been associated with oncogene induction, we examined whether IGF-I activated cellular oncogenes in L6 rat muscle cells, known target cells of IGF-I stimulatory action. Quiescent cells were incubated in serum-free defined medium with IGF-I (Amgen recombinant analog, Thr59) from 5 min to 4 h. 32P-Labeled DNA was first prepared from IGF-I-treated cell poly(A) RNA using avian myeloblastosis virus reverse transcriptase. This labeled probe was hybridized against a blot containing 12 different immobilized oncogene DNAs. The v-fos DNA showed a positive hybridization signal, indicating the presence of c-fos mRNA sequences. Northern analysis with [32P]v-fos DNA revealed a major c-fos mRNA species (2.2 kilobases) induced by treatment of cells with IGF-I (100 ng/ml) or fetal calf serum (15%) for 45 min. We, therefore, measured c-fos induction by cytoplasmic RNA blot hybridization. IGF-I (6.25 ng/ml) stimulated c-fos mRNA 4-fold. Maximum stimulation (18-fold) was seen with 100 ng/ml IGF-I. Peak c-fos induction occurred after 30-min exposure to IGF-I and remained elevated for up to 2 h. Treatment of cells with a high dose of insulin (100 nM) also resulted in a modest (27%) increase in relative levels of c-fos mRNA. The results show that c-fos mRNA is induced by IGF-I in L6 cells. This novel observation suggests that IGF-I action at least in part may be mediated by c-fos, a cellular oncogene thought to play a critical role in cell differentiation and proliferation.

Animals↗

PubMed1987

Relative increase in insulin-like growth factor I messenger ribonucleic acid levels in compensatory renal hypertrophy.

Immunoreactive insulin-like growth factor I (IGF-I) has recently been demonstrated in multiple tissues, including liver, kidney, lung, testes, and brain. Tissue IGF-I levels in hypophysectomized rats are elevated by GH. To examine whether tissue IGF-I production is regulated by local as well as systemic influences, we studied rat kidney IGF-I gene expression in renal compensatory hypertrophy occurring after unilateral nephrectomy. Northern analysis of kidney poly(A) RNA probed with [32P]IGF-I mouse cDNA revealed the presence of a mRNA species 1.3 kilobases in size. Dot hybridization of kidney poly(A) RNA showed that IGF-I mRNA was induced 5- to 6-fold in the kidneys of nephrectomized animals relative to levels in control sham-operated rats. This induction was present 24 h after surgery and continued for at least 7 days after the operation. Kidney radioimmunoassayable IGF-I content was also increased 73% in nephrectomized animals, although this was only apparent on the fourth day after surgery. In contrast, liver IGF-I mRNA levels were comparable in both experimental and control animals, suggesting that the IGF-I induction was specific to the tissue undergoing compensatory growth. Serum IGF-I and GH levels were not altered in nephrectomized and control animals for the duration of the experiments. These studies, therefore, confirm that IGF-I is synthesized in the kidney, and that kidneys undergoing compensatory growth have increased levels of IGF-I mRNA. This phenomenon occurs independently of changes in GH secretion, indicating that paracrine or autocrine factors are involved in the control of renal IGF-I production.

Animals↗

PubMed1987

Insulin-like growth factor I gene expression in GH3 rat pituitary cells: messenger ribonucleic acid content, immunocytochemistry, and secretion.

Insulin-like growth factor I (IGF-I) is present in multiple tissues and cell types. Expression of the IGF-I gene was examined in GH3 cells, a rat pituitary tumor cell line secreting GH and PRL. Increasing concentrations of RNA extracts of GH3 cells yielded a linear increase in hybridization intensity with a 32P-labeled mouse IGF-I cDNA probe. Northern analysis of GH3 cells poly(A) RNA revealed IGF-I mRNA transcripts 1.3, 5.3, and 7.7 kilobases in size. Poly(A) RNA extracts of BALBc/3T3 fibroblasts, a cell line dependent on exogenous somatomedins for DNA synthesis, and of JEG-3 cells, a choriocarcinoma cell line, did not hybridize with the IGF-I cDNA probe. GH3 cells showed positive immunoperoxidase staining using a rabbit anti[Thr59]IGF-I antibody which was largely blocked by prior incubation of the antibody with excess IGF-I. Negligible background peroxidase activity was present in cells incubated with a rabbit nonimmune serum and PBS. Furthermore, BALBc/3T3 fibroblasts showed only weak specific staining with the IGF-I antibody. Finally, GH3 cells secreted IGF-I into the culture medium in a time-dependent fashion, while neither 3T3 nor JEG-3 cells produced detectable medium levels of the peptide after 72 h of incubation. As IGF-I is known to inhibit GH production by the pituitary, the data shown suggest that locally produced IGF-I may regulate GH secretion in an autocrine or paracrine fashion.

Animals↗

PubMed1987

Insulin-like growth factor I action on rat anterior pituitary cells: effects of intracellular messengers on growth hormone secretion and messenger ribonucleic acid levels.

We have previously shown that insulin-like growth factor (IGF-I) suppresses basal and GHRH-induced GH gene transcription. cAMP is a putative intracellular mediator of GHRH action. We, therefore, studied the mechanism of IGF-I action on the somatotroph with or without cAMP activators. Primary rat pituitary cells growing in serum-free medium were treated with IGF-I. GH secretion was measured by RIA, and mRNA levels were measured by hybridization to [32P]GH cDNA. 8-Bromo-cAMP (8-Br-cAMP; 0.625 mM) stimulated GH mRNA levels after 72 h by 238%. IGF-I (6.5 nM) caused a 64% inhibition of 8-Br-cAMP-stimulated GH mRNA levels and a similar inhibition of GH secretion. This inhibition was time and dose dependent, with maximal (71%) suppression of cAMP-induced GH achieved with 13 nM IGF-I after 72 h. Forskolin (1 microM), a stimulator of adenylate cyclase, stimulated GH secretion (198%) which was inhibited by IGF-I by 42%. 12-O-Tetradecanoylphorbol 13-acetate, (a phorbol ester; 50 nM), a potent activator of protein kinase C, strongly stimulated GH secretion (347%), which was similarly suppressed by IGF-I by 51%. The suppressive action of IGF-I on somatotroph gene expression is unimpaired by direct activation of both cAMP and protein kinase C, suggesting that IGF-I acts upon the GH gene by a mechanism that is not altered by these second messengers. The negative feedback inhibition of physiological concentrations of IGF-I on GH, therefore, appears to override the potent stimulation of GH by these intracellular messengers.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

Identification of human growth hormone messenger ribonucleic acid in pituitary adenoma cells by in situ hybridization.

The technique of in situ hybridization was used to examine human GH gene expression in human GH-secreting pituitary adenoma cells. Five somatotroph adenoma specimens obtained at surgery were dispersed into single cell suspensions. Hybridization experiments were performed on cells immediately after dispersal or on cells cultured for 48-72 h in a defined serum-free medium. Tritiated GH cDNA was used to probe fixed cells, and hybridization was determined by liquid autoradiography. Of the freshly dispersed adenoma cells probed with GH cDNA, more than 70% contained GH mRNA, as determined by counting silver grains per cell. Significant cellular grain counts were obtained for GH cDNA-probed cells from all five tumors, while negative controls showed negligible silver grain counts. In cultured cells derived from three of five tumors, an average of 40% contained detectable GH mRNA. Therefore, quantitative in situ hybridization is a useful technique to demonstrate the expression of GH mRNA in human pituitary adenoma cells.

Adenoma↗

PubMed1987

Ectopic pituitary and hypothalamic hormone syndromes.

The pathophysiology and diagnosis of ectopic hormone syndromes are discussed, and a classification of hypothalamic and pituitary ectopic syndromes is provided. Ectopic hypothalamic syndromes resulting from tumor elaboration of GRH, GnRH, CRF, and SRIF and ectopic pituitary hormone hypersecretion of GH, PRL, and TSH are reviewed comprehensively. A practical approach to the clinical work-up and management of these newly described disorders is provided.

Hamartoma↗

PubMed1987

Endocrine function in amyotrophic lateral sclerosis. A review.

Endocrine and metabolic disturbances found in patients with ALS are reviewed. Pancreatic function, carbohydrate tolerance, calcium metabolism, testicular and ovarian thyroid and pituitary function are discussed. It is difficult to interpret these various metabolic dysfunctions as being either an epiphenomenon of ALS or possibly a clue to etiology of the disease. The data are reviewed and interpreted with these constraints.

Amyotrophic Lateral Sclerosis↗

PubMed1987

Acromegaly update--etiology, diagnosis and management.

Acromegaly is a disease with unique clinical manifestations. Its confirmatory diagnosis, however, requires basal and dynamic tests of growth hormone secretion. The measurement of circulating levels of somatomedin C has been a valuable addition to the diagnostic armamentarium. We review the etiology of acromegaly, with particular reference to the different histochemical and ultrastructural forms of somatotropic adenomas and their respective clinical behaviors. Ectopic sources of growth hormone-releasing hormone and of growth hormone itself are now well-recognized, though unusual, causes of acromegaly. The treatment of acromegaly is often problematic and far from uniformly successful. Initial enthusiasm for the results of surgical treatment has now been tempered by reports of increasing rates of recurrence on long-term follow-up. The roles of irradiation and pharmacotherapy are reviewed with particular emphasis on the use of bromocriptine, which has added a new dimension to the control of the somatic and metabolic manifestations of hypersomatotropism. Studies have been done recently using a long-acting somatostatin analog with encouraging results.

Acromegaly↗

PubMed1986

Bromocriptine inhibits incorporation of [3H]thymidine into rat pituitary tumor cells.

The effects of bromocriptine on GH3 pituitary tumor cell [3H]thymidine incorporation were studied. Cells were grown in the presence of bromocriptine, then exposed to a short-term pulse of [3H]thymidine in serum-free medium containing deoxycytidine (10 microM) to prevent deoxythymidine triphosphate (dTTP) pooling. After 48 h exposure to bromocriptine, basal prolactin (PRL)-secretion during 45 min was inhibited by 50% by 10 microM bromocriptine and thyroid releasing hormone-induced PRL stimulation was suppressed. Incorporation of radiolabelled thymidine into acid-precipitable DNA increased progressively from 15 to 60 min and was abolished by simultaneous incubation with excess unlabelled thymidine (100 microM). Bromocriptine (10 microM) inhibited incorporation of 5-50 microM [3H]thymidine, but this was not reversed by simultaneous incubation with metoclopramide (10 microM). Aminopterin, an inhibitor of endogenous de novo DNA synthesis, stimulated [3H]thymidine incorporation twofold and this increased DNA salvage pathway activity was also blocked by bromocriptine. As incorporation of [3H]thymidine into acid-soluble cell nucleotides was also inhibited by bromocriptine, the data suggest that in these cells the drug inhibits thymidine kinase activity, a salvage pathway of DNA synthesis.

Animals↗

PubMed1986

Isolation and characterization of rat-mouse somatic cell hybrids secreting growth hormone and prolactin.

Interspecific somatic cell hybrid clones have been isolated and characterized in order to study growth hormone (GH) and prolactin (PRL) gene expression. Rat pituitary tumor cells (GH3, 69 chromosomes) secreting rat GH and PRL were grown for 48 h together with nonhormone secreting, aminopterin-sensitive murine fibroblast cells (LMTK-, 55 chromosomes) and fused using polyethylene glycol. Resultant heterokaryons were selected in hypoxanthine-aminopterin-thymidine (HAT) medium and cloned. Five clones produced rat GH and PRL. Hormone-producing hybrids morphologically resembled the mouse parent fibroblast. Hybrids grew in monolayers and contained 80-142 chromosomes, and marker chromosomes for both rat (small submetacentric) and mouse (bi-armed and large true metacentric) were identified. The interspecific nature of the hybrids was further confirmed by the presence of both rat and mouse adenosine deaminase and superoxide dismutase isozymes. Using specific antisera and indirect immunoperoxidase staining, both hybrid clones and GH3 rat parental cells stained positively for rat GH and PRL, while the murine fibroblast parental cells were negative. Hormone production by the hybrids has been sustained for over twenty subcultures; secretion rates were initially 150 ng PRL and 321 ng GH/10(6) cells/24 h and are currently 100 ng PRL and 90 ng GH/10(6) cells/24 h. Parental GH3 rat cells secreted 720 ng PRL and 660 ng GH/10(6) cells/24 h. Exposure of hybrids to KCl (50 mM) resulted in acute stimulation of rat PRL, but not rat GH release, and long-term incubation with thyrotropin-releasing hormone (TRH, 80 nM) stimulated PRL secretion. Hormone-dependent modulation of PRL secretion was transferred to the hybrid cell thus enabling the model to be used in studying regulation of PRL gene expression.

Animals↗

PubMed1986

In vitro secretion of deoxycorticosterone by a benign Leydig cell tumor of the testis.

We evaluated the in vitro steroidogenic potential of a benign Leydig cell tumor of the testis. Tumor tissue was found to secrete deoxycorticosterone, progesterone, 17 alpha-hydroxyprogesterone, estradiol and testosterone into the medium. No corticosterone or aldosterone was detected. The ratio of progesterone to 17 alpha-hydroxyprogesterone was 4:1, consistent with a partial enzymatic block of 17 alpha-hydroxylase. The finding of deoxycorticosterone indicates the presence of 21-hydroxylase activity within the tumor. The high local levels of estrogen produced by Leydig cell tumors may induce this enzyme system and, together with the elevated concentrations of progesterone serving as substrate, may provide a favorable hormonal milieu for extra-adrenal deoxycorticosterone production by these neoplasms.

Adult↗

PubMed1986

Insulin regulation of rat growth hormone gene transcription.

We have previously shown that insulin suppresses growth hormone (GH) messenger (m) RNA levels in rat pituitary cells. To further delineate the molecular mechanism of insulin action, the effect of insulin treatment on GH gene transcription rates was examined in GH3 pituitary cells grown in serum-free defined medium. A transcriptional run-off assay was performed when intact isolated nuclei were allowed to continue RNA synthesis in an in vitro reaction. Specific incorporation of [32P]GTP into RNA was quantified by hybridization to rat GH complementary (c) DNA. Hybridization efficiency was measured with an internal [3H]cRNA standard and ranged from 30 to 48%. Alpha-amanitin (1 microgram/ml) inhibited total transcription, and excess unlabeled rat pituitary mRNA (250 ng) competitively inhibited GH mRNA hybridization by greater than 80%. Insulin (0.7 nM) inhibited new GH mRNA synthesis, and maximal inhibition (30% of control) was observed with 7 nM insulin after 4 h treatment. The inhibitory effects of insulin on new GH mRNA synthesis were abolished by both insulin-receptor-antiserum and by guinea-pig anti-insulin serum. The results show that insulin exerts a rapid suppression of new GH mRNA synthesis. These data provide evidence for the direct transcriptional regulation of the GH gene by insulin.

Animals↗

PubMed1986

Insulin-like growth factor I action on rat anterior pituitary cells: suppression of growth hormone secretion and messenger ribonucleic acid levels.

Somatomedin preparations have previously been shown to suppress GH release. The effects of a synthetic recombinant human insulin-like growth factor analog (IGF-I; Thr 59) were, therefore, tested on long term GH secretion by male rat pituitary monolayer cell cultures grown in serum-free defined medium. IGF-I (3.25 nM) maximally suppressed basal GH secretion for up to 72 h by 66%, with an ED50 of 0.1 nM. Human pancreatic GRF-(1-44) (GHRH; 1 nM) stimulated GH secretion by 230% during 72 h. IGF-I (0.13 nM) suppressed GHRH-stimulated GH secretion by 30% (P less than 0.005). IGF-I (0.625 nM) completely abolished stimulation of GH by GHRH (1 nM), while higher doses of IGF-I (up to 6.5 nM) actually suppressed GH secretion even in the presence of GHRH (up to 1 nM). The depletion of intracellular GH levels in GHRH-treated cells was reversed by IGF-I (3.25 nM). PRL secretion was not altered in the same cells by IGF-I. Equivalent doses of epidermal growth factor and fibroblast growth factor did not alter basal or GHRH-stimulated GH secretion. Nitrocellulose dot hybridization of immobilized pituitary cell RNA extracts with rat GH [32P]cDNA showed that cellular GH mRNA levels were lowered in IGF-I-treated cells in a dose-dependent manner. Maximal suppression of GH mRNA was achieved with 0.65 nM IGF-I. IGF-I also inhibited the 3-fold stimulation of GH mRNA induced by 1 nM GHRH. The data show that IGF-I directly modulates GH gene expression at the level of the somatotroph by inhibiting basal and GHRH-stimulated GH secretion and GH mRNA levels during 72 h. These effects may occur at different postranscriptional sites. Alternatively, they may result from a direct inhibition of IGF-I on GH gene transcription.

Animals↗

PubMed1986

Autoregulation of pituitary growth hormone messenger ribonucleic acid levels in rats bearing transplantable mammosomatotrophic pituitary tumors.

Female Wistar-Furth rats were implanted sc with GH3 rat pituitary tumor cells. Tumors were palpable by 4 weeks, and animals were killed periodically from 5-9 weeks. Tumor-bearing rats (n = 10) were heavier than their respective controls, reaching a weight of 372 +/- 3 by 9 weeks vs. 195 +/- 5 g in controls (mean +/- SE). Circulating serum GH levels increased in tumor-bearing animals from 218 +/- 50 to 9067 +/- 962 ng/ml. Serum insulin-like growth factor I (IGF-I) levels were elevated 3-fold in tumor-bearing rats. After death, pituitary glands were excised, and their total RNA was extracted. GH mRNA was assayed by dot hybridization of immobilized pituitary RNA with [32P]cDNA for rat GH. The hybridization signal was quantified by densitometry of autoradiographs. Pituitary rat GH mRNA levels were suppressed 50% in tumor-bearing animals after 5 weeks. By the end of the 9-week period, pituitary GH mRNA levels were undetectable in tumor-bearing animals. The results show that GH tumor-bearing animals exhibit high levels of circulating GH and IGF-I and suppressed endogenous pituitary GH mRNA levels. This may be caused by autoregulation of pituitary GH gene expression either at the level of the hypothalamus or by a direct effect of GH on the pituitary. Alternatively, the elevated levels of IGF-I may be responsible for the suppression of pituitary GH gene expression .

Actins↗

PubMed1986

Insulin-like growth factor-I action on hypothyroid rat pituitary cells: suppression of triiodothyronine-induced growth hormone secretion and messenger ribonucleic acid levels.

T3 stimulates in vitro GH secretion, whereas somatomedins have been shown to suppress GH. We, therefore, tested the effects of a recombinant human insulin-like growth factor analog (IGF-I; Thr 59) on T3-induced GH secretion. Pituitary monolayer cultures were derived from 4- to 7-week surgically thyroidectomized male rats and grown in hypothyroid medium stripped of T3 and T4. Hypothyroid pituitary cell monolayers secreted low levels of GH (200 ng/ml X 72 h). GH secretion was stimulated (185% of T3-free controls) by the addition of T3 (0.1 nM) during 48 h of incubation. IGF-I (up to 13 nM) did not alter basal GH secretion, but inhibited the induction of GH by T3. IGF-I (0.65 nM) suppressed the 3.5-fold induction of GH by 0.25 nM T3 by 35% (p less than 0.001), whereas maximal (68%) GH suppression was seen with 6.5 nM IGF-I (p less than 0.001). The inhibition of T3-induced GH by IGF-I occurred after 24 h. By 72 h, IGF-I (3.25 nM) suppressed GH stimulation by up to 1 nM T3 [213 +/- 12 (+/- SE) vs. 88 +/- 8 ng GH/10(4) cells]. Insulin, epidermal growth factor, and fibroblast growth factor did not alter the T3-induced GH secretion. GH mRNA was measured by agarose gel blot hybridization analysis and nitrocellulose dot blot hybridization of cytoplasmic RNA with rat GH [32P]cDNA. T3 (0.25 nM) stimulated the hybridization of immobilized pituitary cell RNA extracts, indicating an almost 3-fold increase in rat (r) GH mRNA levels; IGF-I (3.25 nM) suppressed the T3-induced rGH mRNA content of pituitary cells from thyroidectomized rats by 50% during 72 h of incubation. Maximal suppression of rGH mRNA induced by 0.25 nM T3 was achieved with 6.5 nM IGF-I (35% of T3-treated cells). These results show that IGF-I does not alter low basal GH secretion in pituitary cells from hypothyroid rats. IGF-I does, however, block the T3-induction of GH secretion and suppresses GH mRNA levels stimulated by T3. As T3 is known to directly stimulate GH gene transcription, IGF-I may suppress T3 action on GH at a posttranscriptional site.

Animals↗