It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.
Animal ; Cells, Cultured ; Corticotropin/secretion* ; Cytokines/pharmacology ; Cytokines/metabolism* ; Inflammation Mediators/pharmacology ; Inflammation Mediators/metabolism* ; Male ; Peptides/pharmacology ; Peptides/metabolism* ; Pituitary Gland/metabolism* ; Pituitary Gland/drug effects ; Pituitary Gland/cytology ; Prolactin/secretion* ; Rats ; Rats, Inbred WF ; Somatotropin/secretion*

It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.
Animal ; Cells, Cultured ; Corticotropin/secretion* ; Cytokines/pharmacology ; Cytokines/metabolism* ; Inflammation Mediators/pharmacology ; Inflammation Mediators/metabolism* ; Male ; Peptides/pharmacology ; Peptides/metabolism* ; Pituitary Gland/metabolism* ; Pituitary Gland/drug effects ; Pituitary Gland/cytology ; Prolactin/secretion* ; Rats ; Rats, Inbred WF ; Somatotropin/secretion*

Lymphocytic hypophysitis is a rare inflammatory disorder which is caused by autoimmune destruction of the pituitary gland. Almost all reported cases have been in women and the disease is often associated with pregnancy. We describe here the first male case of lymphocytic hypophysitis in Korea. The patient presented with headache, impotence, decreased libido, and deteriorated vision. Endocrinologic studies showed panhypopituitarism, and pituitary MRI imaging revealed a homogeneously enhanced pituitary mass with a thickened stalk. Treatment with prednisolone and thyroid hormone for five months was ineffective. Transsphenoidal resection of the pituitary mass was performed successfully with normalization of the visual field defect. Histologic examination revealed diffuse lymphocytic infiltration with dense collagenous fibrosis, consistent with lymphocytic hypophysitis. Lymphocytic hypophysitis should be considered in differential diagnosis even in men with hypopituitarism and an enlarged pituitary gland.
Adult ; Autoimmune Diseases/diagnosis* ; Autoimmune Diseases/pathology ; Autoimmune Diseases/surgery ; Eosinophilia ; Female ; Human ; Korea ; Lymphocytes/cytology ; Lymphocytes/immunology* ; Lymphocytes/metabolism ; Magnetic Resonance Imaging ; Male ; Pituitary Diseases/diagnosis* ; Pituitary Diseases/pathology ; Pituitary Diseases/surgery ; Pituitary Gland/pathology* ; Pituitary Gland/surgery ; Pituitary Hormones/metabolism ; Pregnancy

Leydig cells are the major source of androgens in males. Stem cells can be induced to differentiate into androgen-secreting Leydig like cells, whose functions are regulated by the hypothalamus and pituitary, so that they precisely secret the necessary hormones to maintain physiological function. Therefore, the establishment of an effective protocol to induce the differentiation of stem cells into androgen-secreting cells is very helpful for the treatment of hypogonadism caused by abnormalities of Leydig cells. This review outlines the recent findings concerning the differentiation of stem cells into androgen-secreting cells.
Androgens ; secretion ; Cell Differentiation ; physiology ; Humans ; Hypogonadism ; therapy ; Hypothalamus ; physiology ; Male ; Pituitary Gland ; physiology ; Stem Cells ; cytology ; secretion

AIMTo study the effects of Cu2+ on growth hormone (GH) secretion of pig pituitary cells in vivo.

METHODSGland pituitary cells of 32-35 days old pigs were incubated for 48 h in presence of 10% fetal calf serum in DMEM. Cells were treated for 36 h with various concentrations of Cu2+ (0 mg/L, 0.025 mg/L, 0.1 mg/L, 0.4 mg/L, 1.6 mg/L) in serum-free DMEM. Culture medium was collected in 12 h, 24 h, 36 h thereafter for GH measurement and the radioimmunoassay kits were provided by Linco.

RESULTSThe GH concentration was higher in treatments of 0.025 mg/L, 0.1 mg/L, 0.4 mg/L than that of 0 mg/L when the cells were treated with Cu2+ for 24 h, and it was significantly different (P < 0.05) between treatment 0.1 mg/L and treatment 0 mg/L.

CONCLUSIONIt was concluded that the presence of Cu2+ stimulated pig pituitary cells to secret GH in vivo.

Animals ; Cells, Cultured ; Copper ; pharmacology ; Culture Media ; Growth Hormone ; secretion ; Pituitary Gland ; cytology ; drug effects ; metabolism ; Swine

Animals ; Cells, Cultured ; Cyclic AMP ; metabolism ; Pituitary Gland, Anterior ; cytology ; drug effects ; metabolism ; Rats ; Substance P ; pharmacology

Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of sGnRH effect was 1 h. Both of sGnRH and mammalian GnRH (mGnRH) augmented the release of GH and the level of GH mRNA in a dose-dependent manner. The potency of sGnRH on both GH release and GH mRNA level was more pronounced than that of mGnRH. The effects of 1 micromol/L APO (Apomorphine), an agonist of D(1)/ D(2) dopamine receptors, significantly stimulated GH release and GH mRNA synthesis after incubation for 12 h. APO stimulated GH release and GH mRNA abundance in a dose-dependent manner. These results demonstrate that both GnRH and DA directly stimulate GH release and GH mRNA expression at the pituitary level, the actions of GnRH are more potent than that of DA in orange-spotted grouper.
Animals ; Dopamine ; pharmacology ; Gene Expression Regulation ; Gonadotropin-Releasing Hormone ; pharmacology ; Gonadotropins, Pituitary ; metabolism ; Growth Hormone ; biosynthesis ; genetics ; secretion ; Perciformes ; genetics ; metabolism ; Pituitary Gland ; cytology ; metabolism ; Pituitary Hormone-Releasing Hormones ; secretion ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVE: To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL). METHODS: Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (=25) and sham operation group (=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of β-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting. RESULTS: After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 ( < 0.05) and 7 ( < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 ( < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL. CONCLUSIONS JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.
Animals ; Apoptosis ; Arginine Vasopressin ; pharmacology ; Cytoskeleton ; metabolism ; MAP Kinase Signaling System ; Neurons ; cytology ; Pituitary Gland ; cytology ; injuries ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Tubulin ; metabolism

OBJECTIVETo investigate the effect(s) of interleukin-1beta (IL-1beta) on the activity of human growth hormone (hGH) gene promoter in rat pituitary GH3 cells and the molecular mechanism.

METHODSThe method of luciferase reporter gene was used. We firstly established stable GH3 cell line which contains hGH gene promoter -484-30 bp and luciferase reporter gene. After treating these cells with IL-1beta or IL-1beta plus various signaling transduction inhibitors, the concentration of GH in the medium and lysate of GH3 cells and luciferase activities in GH3 cells were measured to reflect the effect of IL-1beta on secretion and synthesis of GH and the promoter activity of the hGH gene and the molecular mechanism. Results IL-1beta (10-10(4)U/ml) increased secretion and synthesis of GH. IL-1beta at levels of 10(2)-10(4) U/ml promoted the luciferase expression in stable GH3 cells, and the maximal action was 1.61 times of the control (P < 0.001). Among the inhibitors of intracellular signaling transduction pathways, mitogen-activated protein kinases (MAPK) inhibitor PD98059 (40 micromol/L) and p38 MAPK inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-1beta, and phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 (10 micromol/L) partly blocked the induction of IL-1beta. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1beta induction of hGH promoter activity. The stimulatory effect of IL-1beta was abolished following deletion of the -196 to -132 bp fragment.

CONCLUSIONSIL-1beta increases the activity of hGH gene promoter in rat pituitary GH3 cells. This stimulatory effect of IL-1beta appears to require the intracellular MAPK, p38 MAPK, and PI3-K dependent signaling pathways. The effect of IL-1beta requires the promoter sequence that spans the -196 to -132 bp fragment of the gene, but it is unrelated to Pit-1 protein.

Animals ; Cell Line ; Chromones ; pharmacology ; Flavonoids ; pharmacology ; Genes, Reporter ; Growth Hormone ; biosynthesis ; genetics ; Humans ; Interleukin-1 ; pharmacology ; Luciferases ; metabolism ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; Morpholines ; pharmacology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; Pituitary Gland ; cytology ; enzymology ; metabolism ; Rats ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases

OBJECTIVETo study the effects of cadmium chloride in anterior pituitary and the relation between apoptosis and expression of procaspase-9 mRNA.

METHODSIn vivo studies:40 SD male rats were randomly distributed into four groups which were administered with CdCl2 at different doses by gavage for 6 weeks;

IN VITRO STUDIESthe rats' anterior pituitary cells were primarily cultured for 120 hours, then treated with CdCl2 at the dose of 0, 1.56, 3.12, 6.25, 12.50, 25.00, 50.00, 100.00 micromol/L for 6 hours; The indices included: expression of procaspase-9 mRNA, detection of apoptosis with TUNEL assay.

RESULTSThe results showed the excretion of ACTH, LH seemed to be decreased dramatically and the apoptosis inclined to enhance remarkably, and further more, the expression of procaspase-9 mRNA appeared to be increased significantly as compared with those of the control. It was show that a dose-effect relationship between the CdCl2 dosing and indices above with the regression analysis and a linear correlation between the mean gray value of apoptosis cell and the relative gray value of procaspase-9 mRNA positive cell. The results indicated that damnification, for example, apoptosis could be caused by certain dose of CdCl2 in anterior pituitary cells with dose dependent manner. Caspase-9 might play a role in the occurrence of apoptosis.

CONCLUSIONIt was suggested that cadmium could induce apoptosis of anterior pituitary both in vivo and in vitro in the manner of dose-dependent, and caspase-9 might play a role during above processes.

Animals ; Apoptosis ; drug effects ; Cadmium Chloride ; administration & dosage ; toxicity ; Caspase 9 ; genetics ; Cells, Cultured ; Dose-Response Relationship, Drug ; Male ; Pituitary Gland, Anterior ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects