A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.
Humans ; Pituitary Hormones/metabolism* ; Luteinizing Hormone ; Follicle Stimulating Hormone ; Prolactin ; Pituitary Gland/metabolism*

OBJECTIVETo evaluate the distribution and expression of peroxisome proliferator activated receptor gamma (PPAR-gamma) in human pituitary adenomas.

METHODSThirty eight consecutive surgically resected pituitary adenomas and 5 normal pituitary tissues were enrolled in the study. Immunohistochemistry was used to confirm the distribution of PPAR-gamma. Expression of PPAR-gamma was evaluated by Western blot.

RESULTSPPAR-gamma immunoreactivity was located in the nucleoli of pituitary adenoma cells. PPAR-gamma was expressed in all human pituitary adenomas and normal pituitary tissues. Its expression in pituitary adenomas was significantly higher than in normal pituitary tissues (P < 0.01), and its expression in ACTH-secreting adenomas was significantly higher than in any other type of pituitary adenomas (P < 0.05).

CONCLUSIONSPPAR-gamma may play an important role in the generation, growth, and invasion of human pituitary adenomas. It may become a novel therapeutic target for these tumors.

ACTH-Secreting Pituitary Adenoma ; metabolism ; Adult ; Female ; Humans ; Male ; Middle Aged ; PPAR gamma ; biosynthesis ; metabolism ; Pituitary Gland ; metabolism ; Pituitary Neoplasms ; metabolism

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*

Bone is a dynamic tissue undergoing life-long remodeling, a process of bone resorption by osteoclast and bone formation by osteoblast, regulated by diverse hormones including estrogen. Recently, several pituitary hormones have been identified as a modulator of this process. Here, we reviewed the role of thyroid stimulating hormone signaling per se in bone metabolism.
Bone Remodeling ; Bone Resorption ; Estrogens ; Metabolism* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Pituitary Hormones ; Thyroid Gland* ; Thyrotropin*

Bone is a dynamic tissue undergoing life-long remodeling, a process of bone resorption by osteoclast and bone formation by osteoblast, regulated by diverse hormones including estrogen. Recently, several pituitary hormones have been identified as a modulator of this process. Here, we reviewed the role of thyroid stimulating hormone signaling per se in bone metabolism.
Bone Remodeling ; Bone Resorption ; Estrogens ; Metabolism* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Pituitary Hormones ; Thyroid Gland* ; Thyrotropin*

Metallothionein (MT) family, intracellular zinc binding proteins, has been suggested to play an important regulatory role in zinc metabolism. The present study utilized light and confocal microscopic methods to investigate the expression pattern of MT-1, 2 and to determine the distribution and extent of colocalization of MT-1, 2 relative to subpopulations of S100 positive folliculostellate (FS) cells and somatotrophs in normal rat anterior pituitary. By light microscopy, MT-1, 2 immunoreactivity was observed both in pars intermedia and pars distalis of anterior pituitary. Confocal microscopy revealed that most MT immunoreactivity was colocalized in S100 positive FS cells, not in somatotrophs. This is the first report that FS cells in pars distalis contain MT-1, 2. These results suggest that MT family may be involved in regulation of hypophyseal endocrine functions and can be used as new markers of FS cells.
Animals ; Carrier Proteins ; Humans ; Immunohistochemistry ; Metabolism ; Metallothionein ; Microscopy ; Microscopy, Confocal ; Pituitary Gland, Anterior* ; Rats* ; Somatotrophs ; Zinc

OBJECTIVETo investigate the expression and significance of CD151 in pituitary adenomas.

METHODSThirty-six pituitary adenomas were collected immediately after surgery together with five normal pituitary tissue. Real time-PCR, Western blot and immunohistochemistry analysis were performed to detect the expression of CD151 mRNA and protein in thirty-six pituitary adenomases and five normal pituitary tissues.

RESULTSThe expression of CD151 in all pituitary adenomases was observed to be significantly higher than that in normal pituitary tissues by Western blot, real time PCR, and immunohistochemistry analysis (P < 0.01). The expression levels of protein and mRNA in invasive pituitary adenomas were much higher than those in non-invasive pituitary adenomas (P < 0.01).

CONCLUSIONThe results suggested that the expression of CD151 was closely correlated with malignant degree of pituitary adenomas, which indicated the expression of CD151 was intimately correlated with occurrence and development of pituitary adenomas. Detecting CD151 might be a vital index to predict prognosis of pituitary adenomas.

Adenoma ; metabolism ; Blotting, Western ; Humans ; Immunohistochemistry ; Pituitary Gland ; pathology ; Pituitary Neoplasms ; metabolism ; Prognosis ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Tetraspanin 24 ; metabolism

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

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