scholarly journals Hes1 and Hes5 Control the Progenitor Pool, Intermediate Lobe Specification, and Posterior Lobe Formation in the Pituitary Development

2007 ◽  
Vol 21 (6) ◽  
pp. 1458-1466 ◽  
Author(s):  
Aya Kita ◽  
Itaru Imayoshi ◽  
Masato Hojo ◽  
Masashi Kitagawa ◽  
Hiroshi Kokubu ◽  
...  

Abstract The pituitary gland is composed of two distinct entities: the adenohypophysis, including the anterior and intermediate lobes, and the neurohypophysis, known as the posterior lobe. This critical endocrine organ is essential for homeostasis, metabolism, reproduction, and growth. The pituitary development requires the control of proliferation and differentiation of progenitor cells. Although multiple signaling molecules and transcription factors are required for the proper pituitary development, the mechanisms that regulate the fate of progenitor cells remain to be elucidated. Hes genes, known as Notch effectors, play a crucial role in specifying cellular fates during the development of various tissues and organs. Here, we report that mice deficient for Hes1 and Hes5 display severe pituitary hypoplasia caused by accelerated differentiation of progenitor cells. In addition, this hypoplastic pituitary gland (adenohypophysis) lacks the intermediate lobe and exhibits the features of the anterior lobe only. Hes1 and Hes5 double-mutant mice also lack the neurohypophysis (the posterior lobe), probably due to incomplete evagination of the diencephalon. Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis.

1985 ◽  
Vol 101 (1) ◽  
pp. 305-311 ◽  
Author(s):  
P Kristensen ◽  
L S Nielsen ◽  
J Grøndahl-Hansen ◽  
P B Andresen ◽  
L I Larsson ◽  
...  

We immunocytochemically stained rat pituitary glands using antibodies against plasminogen activators of the tissue type (t-PA) and the urokinase type (u-PA). A large population of endocrine cells in the anterior lobe of the gland displayed intense cytoplasmic immunoreactivity with anti-t-PA. In some areas of the intermediate lobe we found a weak staining, and we observed weakly staining granular structures in the posterior lobe. Controls included absorption of the antibodies with highly purified t-PA. In addition, SDS PAGE followed by immunoblotting of pituitary gland extracts revealed only one band with an electrophoretic mobility similar to that of t-PA when stained with anti-t-PA IgG. No u-PA immunoreactivity was detected in the rat pituitary gland. Sequential staining experiments using antibodies against growth hormone and t-PA demonstrated that the t-PA-immunoreactive cells constitute a large subpopulation of the growth hormone-containing cells. These findings represent the first direct evidence for the presence of t-PA in cell types other than endothelial cells in the intact normal organism. In this article we discuss the implications of the results for a possible role of t-PA in the posttranslational processing of prohormones.


1934 ◽  
Vol 30 (6) ◽  
pp. 634-634
Author(s):  
P. Badul

The posterior lobe of the pituitary gland in a bull is free of prolan, while in a human it contains prolan. Only here it can be found in that part of the posterior pituitary lobe adjacent to the anterior lobe. In the bull, too, this part of the pituitary gland is completely free of prolan content. Histological examination shows that in humans, this part of the posterior lobe is crossed by bands of cells from the anterior lobe, which consist exclusively of basophilic cells.


2005 ◽  
Vol 19 (3) ◽  
pp. 698-710 ◽  
Author(s):  
Robert D. Ward ◽  
Lori T. Raetzman ◽  
Hoonkyo Suh ◽  
Brandon M. Stone ◽  
Igor O. Nasonkin ◽  
...  

Abstract Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well as to pituitary hypoplasia in adult humans and mice. Some PROP1-deficient patients initially exhibit pituitary hyperplasia that resolves to hypoplasia. To understand this feature and to explore the mechanism whereby PROP1 regulates anterior pituitary gland growth, we carried out longitudinal studies in normal and Prop1-deficient dwarf mice from early embryogenesis through adulthood, examining the volume of Rathke’s pouch and its derivatives, the position and number of dividing cells, the rate of apoptosis, and cell migration by pulse labeling. The results suggest that anterior pituitary progenitors normally leave the perilumenal region of Rathke’s pouch and migrate to form the anterior lobe as they differentiate. Some of the cells that seed the anterior lobe during organogenesis have proliferative potential, supporting the expansion of the anterior lobe after birth. Prop1-deficient fetal pituitaries are dysmorphic because mutant cells are retained in the perilumenal area and fail to differentiate. After birth, mutant pituitaries exhibit enhanced apoptosis and reduced proliferation, apparently because the mutant anterior lobe is not seeded with progenitors. These studies suggest a mechanism for Prop1 action and an explanation for some of the clinical findings in human patients.


1983 ◽  
Vol 97 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
A Granelli-Piperno ◽  
E Reich

We studied plasminogen activator (PA) of the rat pituitary gland in organ and cell monolayer culture. Both anterior and intermediate lobes contain, synthesize and secrete a mixture consisting of the two known types of PA: urokinase and so-called tissue PA. Both enzymes were formed essentially by all PA secreting cells, and PA was identified specifically in mammotrophs, corticotrophs, and luteinizing hormone containing gonadotrophs. Pituitary PA production was modulated on exposure to a variety of biological effectors: anterior lobe PA secretion was stimulated by agents that raised intracellular cAMP concentration; his process depended on de novo enzyme synthesis. Enzyme production was repressed by androgens and glucocorticoids. When anterior lobe cultures were maintained in plasminogen-free media, the extracellular, secreted forms of ACTH consisted almost exclusively of the high molecular weight forms (31,000 and 23,000); the smaller forms (13,000 and 4,500) were also found in the extracellular medium of cultures supplemented with plasminogen. In contrast, the size distribution of intracellular ACTH species was unaffected by the presence of plasminogen. These results resemble those previously obtained with pancreatic islets and are consistent with the possibility that plasmin, generated by PA secretion, participates in prohormone processing. PA synthesis in intermediate lobe explants was stimulated by exposure to dibutyryl cAMP, and repressed by hydrocortisone. In accordance with the dopaminergic control of intermediate lobe function in some vertebrates, apomorphine strongly repressed PA synthesis in intermediate, but not anterior lobe cultures.


1965 ◽  
Vol 48 (2) ◽  
pp. 177-185 ◽  
Author(s):  
L. Barnafi ◽  
H. Croxatto

ABSTRACT The distribution and individual variation of vasopressor and oxytocic activities in the hypothalamus, posterior and anterior lobe of the pituitary gland of 13 women and 15 men were studied. The results showed great individual variation of vasopressor and oxytocic activities in the posterior and anterior lobes, whereas in the hypothalamus a relatively constant hormonal activity was found. No significant sex differences were noted with respect to the content of the vasopressor and oxytocic activities in the hypothalamus and posterior lobe. In the anterior lobe of the female, a higher vasopressor activity was found than in males. No relationship could be established between the distribution of these activities and the pathological condition preceding death.


1996 ◽  
Vol 148 (2) ◽  
pp. 193-196 ◽  
Author(s):  
T Pawełczyk ◽  
M Pawlikowski ◽  
J Kunert-Radek

Abstract The effect of TRH on cell proliferation in the anterior lobe of the pituitary is well known and documented. On the other hand, there are no data on the effects of TRH on the intermediate lobe of the pituitary gland. The aim of this study was to investigate the effect of TRH and its analogues (pGlu-His-Gly, pGlu-His-Gly-NH2) on cell proliferation in the intermediate pituitary lobe. The bromodeoxyuridine technique was used to detect the proliferating cells. It was found that TRH stimulated cell proliferation 24 h after a single injection at a dose of 100 μg/kg body weight. The TRH analogues did not exert any significant stimulatory effect either 12 h or 24 h after the injection. The second experiment was carried out to distinguish the probable mechanism of the action of TRH. The effects of TSH and prolactin (PRL) on intermediate lobe cell proliferation were examined. It was found that both PRL and TSH exerted a significant stimulatory effect 24 h after a single s.c. injection of PRL at a dose of 150 IU/kg body weight or TSH at a dose 20 IU/kg body weight. It therefore appears that the stimulatory effect of TRH on intermediate pituitary lobe cell proliferation is mediated by PRL and TSH. Journal of Endocrinology (1996) 148, 193–196


Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2342-2352 ◽  
Author(s):  
Shuo Li ◽  
Ivana Bjelobaba ◽  
Zonghe Yan ◽  
Marek Kucka ◽  
Melanija Tomić ◽  
...  

Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show that the rat pituitary gland expresses mRNA and protein transcripts of pannexins 1 and 2 but not pannexin 3. Pannexin 1 was more abundantly expressed in the anterior lobe, whereas pannexin 2 was more abundantly expressed in the intermediate and posterior pituitary. Pannexin 1 was identified in corticotrophs and a fraction of somatotrophs, the S100-positive pituicytes of the posterior pituitary and AtT-20 (mouse pituitary adrenocorticotropin-secreting cells) and rat immortalized pituitary cells secreting prolactin, whereas pannexin 2 was detected in the S100-positive folliculostellate cells of the anterior pituitary, melanotrophs of the intermediate lobe, and vasopressin-containing axons and nerve endings in the posterior lobe. Overexpression of pannexins 1 and 2 in AtT-20 pituitary cells enhanced the release of ATP in the extracellular medium, which was blocked by the gap junction inhibitor carbenoxolone. Basal ATP release in At-T20 cells was also suppressed by down-regulating the expression of endogenous pannexin 1 but not pannexin 2 with their short interfering RNAs. These results indicate that pannexins may provide a pathway for delivery of ATP, which is a native agonist for numerous P2X cationic channels and G protein-coupled P2Y receptors endogenously expressed in the pituitary gland.


2006 ◽  
Vol 20 (11) ◽  
pp. 2898-2908 ◽  
Author(s):  
Lori T. Raetzman ◽  
Bayly S. Wheeler ◽  
Shelley A. Ross ◽  
Paul Q. Thomas ◽  
Sally A. Camper

Abstract Normal pituitary gland development requires coordination between maintenance of progenitor cell pools and selection of progenitors for differentiation. The spatial and temporal expression of Notch2 during pituitary development suggested that it could control progenitor cell differentiation in the pituitary. Consistent with this idea, Notch2 is not expressed in Prop1 mutants, and anterior pituitary progenitors in Prop1 mutants appear to be unable to transition from proliferation to differentiation properly, resulting in anterior lobe failed cell specification and evolving hypoplasia. To test the function of Notch2 directly, we used the αGSU subunit promoter to express activated NOTCH2 persistently in pre-gonadotropes and pre-thyrotropes of transgenic mice. At birth, there is a small reduction in the population of fully differentiated thyrotropes and almost no fully differentiated gonadotropes. The temporal and spatial expression of Hey1 suggests that it could be a mediator of this effect. Gonadotropes complete their differentiation program eventually, although expression of LH and FSH is mutually exclusive with NOTCH2 transgene expression. This demonstrates that activated Notch2 is sufficient to delay gonadotrope differentiation, and it supports the hypothesis that Notch2 regulates progenitor cell differentiation in the pituitary gland.


1924 ◽  
Vol 1 (3) ◽  
pp. 313-321
Author(s):  
E. A. SPAUL

1. Acceleration of the metamorphosis of frog tadpoles is induced by injections of commercial extracts of the anterior lobe pituitary gland extract. 2. The acceleration of metamorphosis produced by iodine in solution in suitable concentrations is not so great as that produced by injections of the anterior pituitary extract. 3. Further increase in the acceleration occurs when the injected specimens are kept in suitable concentrations of iodine solution. 4. The sequence of changes is similar to that observed in the accelerated transformation of tadpoles produced by thyroid or iodine diet. 5. The highest mortality, greatest reduction in size, and most rapid transformation occurs in the highest concentration of iodine, and this is still greater in injected animals kept in iodine solutions. 6. The younger the tadpole the less chance is there of completing metamorphosis under the accelerating stimulus of injected anterior lobe or iodine. 7. There is a paling effect after initial injection less marked in older specimens which is possibly due to inhibiting influence on the posterior lobe of excess of anterior lobe secretion. Idoine has no definite pigment action. 8. Iodine appears to act independently of the anterior lobe injection in the tadpole, the acceleration being apparently the sum of their separate actions.


2008 ◽  
Vol 20 (1) ◽  
pp. 175
Author(s):  
P. Tinnanooru ◽  
E.-B. Jeung

Estrogen (E2; estradiol) plays a key role in the regulation of many pituitary hormones. It exerts its effects by binding to the intracellular estrogen receptor (ER), which then functions as a transcription factor. Although E2 has been shown to regulate calbindin-D9k (CaBP-9k) in the female reproductive system of rodents, the effects of E2 on the regulation of CaBP-9k in male rats remains to be elucidated. For investigation of E2-induced regulation of the pituitary CaBP-9k gene, immature male rats were injected with E2 daily for three consecutive days with a dose of 40 µg kg–1 body weight (BW). The expression levels of CaBP-9k mRNA and protein were analyzed by RT-PCR and Western blot analysis, respectively, in the absence and presence of ICI 182 780 (ICI), an E2 antagonist. In addition, the tissue localization of CaBP-9k was determined by immunohistochemistry. CaBP-9k was localized in the cytoplasm of a specific cell type (acidophils) in the anterior lobe of the pituitary gland and highly expressed in the intermediate lobe. Exposure to E2 increased the number of cells that stained positive for CaBP-9k. For determination of which ER subtype is involved in CaBP-9k regulation in the pituitary, the immature rats were treated with 1 mg kg–1 BW propyl pyrazole triol (PPT, an ER-α-selective ligand) or diarylpropionitrile (DPN, an ER-β-selective ligand) for three days. The data were analyzed by the non-parametric procedure of the Kruskal-Wallis test, followed by Dunnett's test for two-pair comparisons. Pituitary CaBP-9k expression was mainly mediated by PPT in immature male rats, whereas no significant alteration of pituitary CaBP-9k gene expression was observed after DPN treatment. In addition, the estrogenicity of PPT in the induction of CaBP-9k expression was completely blocked by an estrogen antagonist, ICI 182 780, indicating that pituitary CaBP-9k expression is solely induced by ER-α. Taken together, these results suggest that pituitary CaBP-9k is induced by estrogen in male rats and its expression is predominantly regulated by ER-α, but not ER-β.


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