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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sox3 is expressed in developing gonads and in the brain. Evolutionary evidence suggests that the X-chromosomal Sox3 gene may be the ancestral precursor of Sry, a sex-determining gene, and Sox3 has been proposed to play a role in sex determination. However, patients with mutations in SOX3 exhibit normal gonadal determination but are mentally retarded and have short stature secondary to growth hormone (GH) deficiency. We used Cre-LoxP targeted mutagenesis to delete Sox3 from mice. Null mice of both sexes had no overt behavioral deficits and exhibited normal GH gene expression. Low body weight was observed for some mice; overgrowth and misalignment of the front teeth was observed consistently. Female Sox3 null mice (-/-) developed ovaries but had excess follicular atresia, ovulation of defective oocytes, and severely reduced fertility. Pituitary (luteinizing hormone and follicle-stimulating hormone) and uterine functions were normal in females. Hemizygous male null mice (-/Y) developed testes but were hypogonadal. Testis weight was reduced by 42%, and there was extensive Sertoli cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of the seminiferous tubules. We conclude that Sox3 is not required for gonadal determination but is important for normal oocyte development and male testis differentiation and gametogenesis.
Mol Cell Biol 2003 Nov
PMID:Sox3 is required for gonadal function, but not sex determination, in males and females. 1458 68

We have previously reported that leptin is expressed in adult rat brain and pituitary gland, though the role of leptin in these sites has not been determined. Leptin mRNA is developmentally regulated in the brain and pituitary of male and female rats during early postnatal development, suggesting a role in the maturation of the brain-pituitary system. Here, we sought to extend our previous studies by evaluating (1) the ontogeny of leptin receptor mRNA levels in rat brain and pituitary and (2) pituitary leptin protein levels in neonatal and pre-pubertal rats. Pituitary leptin concentration was highest shortly after birth (postnatal day (PD) 4, 25 ng/mg protein) and fell significantly throughout postnatal development and into adulthood (PD 60, 3.5 ng/mg protein; P<0.005) coincident with a decline in pituitary leptin mRNA levels. Significant age-related effects on leptin receptor mRNA levels were also observed in the pituitary and the hypothalamus of male and female rats using semi-quantitative RT-PCR analysis. In the pituitary, the short form (OBRa) mRNA levels were highest in neonatal rats (PD 4) but declined throughout postnatal development (PD 4-22) paralleling the fall in pituitary leptin mRNA and protein levels. The long form (OBRb) mRNA levels were unaffected by age between PD 4 and 22. In contrast, hypothalamic, levels of OBRb mRNA were very low to undetectable shortly after birth (PD 4) and rose significantly between PD 4 and 14/22 while levels of OBRa mRNA were not significantly different between PD 4 and 22. Immunohistochemical detection of leptin receptor immunoreactivity (all forms) revealed the presence of OBR-like protein in pituitary and hypothalamus as early as PD 4. Cortical leptin receptor mRNA levels were similar throughout early postnatal development. No gender-related differences in leptin receptor mRNA levels were noted in brain or pituitary. In conclusion, these data, together with our previous work, indicate that the neonatal pituitary gland expresses leptin and leptin receptors at levels far in excess of those observed in mature rats. The pituitary is thus quite different from adipose tissue, hypothalamus and cerebral cortex, in which neonatal leptin expression is lowest at birth. Since neonatal pituitary leptin receptor expression is also elevated, it is possible that pituitary-derived leptin plays some role in the development of the hypothalamic-pituitary system.
Mol Cell Endocrinol 2003 Nov 28
PMID:Leptin receptors are developmentally regulated in rat pituitary and hypothalamus. 1461 55

The effect of freshwater (FW) transfer on growth and on the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis was examined in the tilapia, Oreochromis mossambicus. Tilapia were raised in seawater (SW) for 5 months and then transferred to FW for an additional 40 days. The growth rate of the fish transferred to FW was significantly reduced compared with the growth rate of fish that remained in SW. Plasma levels of GH were significantly elevated in FW-transferred fish, as were plasma IGF-I levels. Pituitary GH and liver IGF-I mRNA levels, on the other hand, were significantly reduced in the fish transferred to FW. There was a significant correlation between body mass and mRNA levels of GH and IGF-I, but not with plasma levels of GH and IGF-I. Fish transferred to FW had significantly higher prolactin (PRL)(177) levels than the SW control fish, although there was no difference in plasma PRL(188) levels. Consistent with the hyperosmoregulatory effects of PRL, mRNA levels of both PRL(177) and PRL(188) were significantly higher in FW-transferred fish than in the fish in SW. These results suggest that transferring tilapia from SW to FW activates the GH/IGF-I axis, but growth is still inhibited, possibly due to the greater metabolic cost of osmoregulation in FW than in SW.
Comp Biochem Physiol B Biochem Mol Biol 2003 Dec
PMID:Effects of transfer from seawater to fresh water on the growth hormone/insulin-like growth factor-I axis and prolactin in the Tilapia, Oreochromis mossambicus. 1466 91

The effects of breed and of recombinant bovine somatotropin (rbST) treatment on growth hormone gene expression were studied in young bulls. The experiment was completely randomized in a [2 x 2]-factorial arrangement, using two levels of rbST (0 or 250 mg/animal/14 days), and two breed groups (Nelore and Simmental x Nelore crossbred). A cDNA encoding Bos indicus growth hormone was cloned and sequenced for use as a probe in Northern and dot blot analyses. Compared to the Bos taurus structural gene, the Bos indicus cDNA was found to begin 21 bases downstream from the transcription initiation site and had only two discrepancies (C to T at position 144-His and T to C at position 354-Phe), without changes in the polypeptide sequence. However, two amino acid substitutions were found for Bubalus spp., which belong to the same tribe. The rbST treatment did not change any of the characteristics evaluated (body and pituitary gland weights, growth hormone mRNA expression level). Crossbred animals had significantly higher body weight and heavier pituitaries than Nelore cattle. Pituitary weight was proportional to body weight in both breed groups. Growth hormone mRNA expression in the pituitary was similar (P>0.075) for both breed and hormonal treatment groups, but was 31.9% higher in the pure Nelore group, suggesting that growth hormone gene transcription regulation differs among these breeds.
Genet Mol Res 2002 Dec 31
PMID:Growth hormone mRNA expression in the pituitary of Bos indicus and Bos taurus x Bos indicus crossbred young bulls treated with recombinant bovine somatotropin. 1496 23

Cholesterol is imported and processed to provide substrate for ovarian steroidogenesis. The Niemann Pick type C-1 gene codes for a glycoprotein that processes low-density lipoproteinimported cholesterol. Mutation of this gene causes marked impairment of export of low-density lipoprotein-derived cholesterol from endosomes, and consequent lysosomal accumulation of the sterol. The BALB/c npc(nih-/-) mouse line, bearing spontaneous mutation of the NPC-1 gene, provides a model for investigation of aberrant endosomal cholesterol transfer in the ovary. Female homozygote mutant mice are infertile, with underdeveloped ovarian follicles, reduced steroidogenesis, no ovulation, and no corpora lutea. Mutant ovaries transplanted under wild-type kidney capsules display both ovulation and formation of corpora lutea. Gonadotropin treatment induces ovulation and restores expression of steroidogenic proteins. Pituitary glands of mutants are hypoplastic, and prolactin expression is dramatically reduced compared with wild-type mice. Both long and short splice variants of the dopamine-D2 receptors are overexpressed in the pituitary of BALB/c npc(nih-/-) mice. Chronic treatment of mutant mice with 17beta-estradiol restores pituitary volume, prolactin expression, and folliculogenetic capability. We conclude that inactivating mutation of Niemann Pick C-1 perturbs the hypothalamic-pituitary-ovarian feedback loop. Reduced estrogens attenuate prolactin expression and alter gonadotropin secretion patterns and interfere with normal ovarian follicular development and ovulation.
Mol Endocrinol 2004 Jul
PMID:Aberrant intracellular cholesterol transport disrupts pituitary and ovarian function. 1510 38

The pleuronectid barfin flounder (Verasper moseri) expresses three forms of gonadotropin-releasing hormone (GnRH) in the brain. To clarify the physiological roles of the respective forms during testicular maturation, changes in brain GnRH mRNA levels and pituitary GnRH peptide levels were examined by real-time quantitative PCR and time-resolved fluoroimmunoassay, respectively. Fish hatched in April 2000. The gonadosomatic index remained low until October 2001 and then rapidly increased in January 2002. Fish continued to grow from hatching through testicular maturation. Fish spermiated in March 2002. The amount of seabream GnRH (sbGnRH) mRNA per brain significantly increased in January 2002 and remained at high levels in March 2002. The amounts of salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II) mRNA per brain did not show significant changes during the experimental periods. Pituitary sbGnRH peptide content significantly increased in March 2002. Pituitary sGnRH peptide and cGnRH-II peptide contents were extremely low compared to sbGnRH peptide levels and showed no significant changes during the experiment. These results indicate that sbGnRH is involved in the testicular maturation of barfin flounder.
Comp Biochem Physiol B Biochem Mol Biol 2004 Aug
PMID:Changes in brain GnRH mRNA and pituitary GnRH peptide during testicular maturation in barfin flounder. 1532 45

Heterotrimeric G proteins of the G(q/11) family transduce signals from a variety of neurotransmitter receptors and have therefore been implicated in several functions of the central nervous system. To investigate the potential role of G(q/11) signaling in behavior, we generated mice which lack the alpha-subunits of the two main members of the G(q/11) family, Galpha(q) and Galpha(11), selectively in the forebrain. We show here that forebrain Galpha(q/11)-deficient females do not display any maternal behavior such as nest building, pup retrieving, crouching, or nursing. However, olfaction, motor behavior and mammary gland function are normal in forebrain Galpha(q/11)-deficient females. We used c-fos immunohistochemistry to investigate pup-induced neuronal activation in different forebrain regions and found a significant reduction in the medial preoptic area, the bed nucleus of stria terminalis, and the lateral septum both in postpartum females and in virgin females after foster pup exposure. Pituitary function, especially prolactin release, was normal in forebrain Galpha(q/11)-deficient females, and activation of oxytocin receptor-positive neurons in the hypothalamus did not differ between genotypes. Our findings show that G(q/11) signaling is indispensable to the neuronal circuit that connects the perception of pup-related stimuli to the initiation of maternal behavior and that this defect cannot be attributed to either reduced systemic prolactin levels or impaired activation of oxytocin receptor-positive neurons of the hypothalamus.
Mol Cell Biol 2004 Sep
PMID:Heterotrimeric G proteins of the Gq/11 family are crucial for the induction of maternal behavior in mice. 1534 67

A subset of transcription factors function as pivotal regulators of cell differentiation pathways. Pituitary transcription factor-1 (Pit-1) is a tissue-specific homeodomain protein that specifies the development of pituitary somatotropes and lactotropes. In this study, adenovirus was used to deliver rat Pit-1 to mouse liver. Pit-1 expression was detected in the majority (50-80%) of hepatocyte nuclei after tail vein injection (2 x 10(9) plaque forming units). Pit-1 activated hepatic expression of the endogenous prolactin (PRL), GH, and TSHbeta genes along with several other markers of lactotrope progenitor cells. Focal clusters (0.2-0.5% of liver cells per tissue section) of periportal cells were positive for PRL by immunofluorescent staining. The PRL-producing cells also expressed proliferating cell nuclear antigen as well as the hepatic stem cell markers (c-Kit, Thy1, and cytokeratin 14). These data indicate that Pit-1 induces the transient differentiation of hepatic progenitor cells into PRL-producing cells, providing additional evidence that transcription factors can specify the differentiation pathway of adult stem cells.
Mol Endocrinol 2005 Apr
PMID:Pituitary transcription factor-1 induces transient differentiation of adult hepatic stem cells into prolactin-producing cells in vivo. 1563 44

Pituitary tumor-transforming gene (PTTG), a securin protein isolated from pituitary tumor cell lines, is highly expressed in invasive tumors and exhibits characteristics of a transforming gene. To determine the role of PTTG in pituitary tumorigenesis, transgenic human PTTG1 was targeted to the mouse pituitary using the alpha-subunit of glycoprotein hormone. Males showed plurihormonal focal pituitary transgene expression with LH-, TSH-, and, unexpectedly, also GH-cell focal hyperplasia and adenoma, associated with increased serum LH, GH, testosterone, and/or IGF-I levels. MRI revealed both pituitary and prostate enlargement at 9-12 months. Urinary obstruction caused by prostatic hyperplasia and seminal vesicle hyperplasia, with renal tract inflammation, resulted in death by 10 months in some animals. Pituitary PTTG expression results in plurihormonal hyperplasia and hormone-secreting microadenomas with profound peripheral growth-stimulatory effects on the prostate and urinary tract. These results provide evidence for early pituitary plasticity, whereby PTTG overexpression results in a phenotype switch in early pituitary stem cells and promotes differentiated polyhormonal cell focal expansion.
Mol Endocrinol 2005 May
PMID:Early multipotential pituitary focal hyperplasia in the alpha-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice. 1567 10

The gastric enterochromaffin-like (ECL) cell plays a major role in the regulation of gastric acid secretion. We have previously described that Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is present on myenteric neurons in the rat and colocalizes with its high-affinity receptor, PAC1, expressed on the surface of gastric ECL cells. The study of ECL cell physiology has been hampered by the inability to isolate and purify ECL cells to homogeneity. Density gradient elutriation alone yields only 65-70% purity of ECL cells. In the present study, we used fluorescence-activated cell sorting (FACS) with a novel fluorescent ligand, Fluor-PACAP-38, for isolating pure ECL cells. FACS was used to isolate ECL cells based on their relatively small size, low density, and ability to bind the fluorescent ligand Fluor-PACAP-38. The sorted cells were unambiguously identified as ECL cells by immunohistochemical analysis using anti-PACAP type-I (PAC1), anti-histidine decarboxylase (HDC), and anti-somatostatin antibodies. Further confocal microscopy demonstrated that Fluor-PACAP-38, a ligand with a higher affinity for PAC1, bound to extracellular receptors of these FACS-purified cells. FACS yielded an average of 2 million ECL cells/4 rat stomachs, and >99% of the sorted cells were positive for PAC1 receptor and HDC expression. The absence of immunohistochemical staining for somatostatin indicated lack of contamination by gastric D cells, which are similar in size and shape to the ECL cells. Internalization of PACAP receptors and a rapid Ca2+ response in purified ECL cells were observed upon PACAP activation, suggesting that these cells are viable and biologically active. These ECL cells demonstrated a dose-dependent stimulation of proliferation in response to PACAP, with a maximum of 30% proliferation at a concentration of 10-7 M. Microarray studies were perfor med to confirm the expression of genes specific for ECL cells. These results demonstrate that rat gastric ECL cells can be isolated to homogeneity by using a combination of density gradient centrifugation, followed by cell sorting using Fluor-PACAP. These techniques now allow microarray studies to be performed in ECL cells to characterize their functional gene expression and will facilitate pharmacological, biochemical, and molecular studies on ECL cell function.
J Mol Neurosci 2005
PMID:PACAP regulation of secretion and proliferation of pure populations of gastric ECL cells. 1596 88


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