Expression, distribution, regulation and function of IGFs in the ovine fetal pituitary

1995 ◽  
Vol 14 (3) ◽  
pp. 323-336 ◽  
Author(s):  
F Lü ◽  
K Yang ◽  
V K M Han ◽  
J R G Challis

ABSTRACT Activation of the fetal pituitary-adrenal axis is crucial for fetal organ maturation and the onset of parturition in sheep. Many factors including corticotrophin-releasing hormone (CRH) and arginine vasopressin secreted from the hypothalamus, and growth factors produced within the pituitary may be involved in the regulation of maturation of the fetal pituitary gland. IGFs have mitogenic and differentiation-promoting capacities in a variety of organs and are synthesized as paracrine factors within developing tissues. However, there is little information concerning the synthesis, distribution, regulation and function of IGFs in the fetal pituitary gland at different times during pregnancy. Therefore, we have localized IGF-I and IGF-II mRNAs and peptides, and determined the effect of cortisol on the level of IGF-II mRNAs in the pituitary glands of developing sheep fetuses. We examined the possible effects of IGFs on corticotroph function in cultures of adenohypophysial cells from term fetuses. Seven species of IGF-II transcripts of 1·2–6·0 kb were identified by Northern blot analysis in the pituitary gland of fetuses between day 60 of gestation and term (day 145). The levels of IGF-II mRNAs did not change significantly during pregnancy, although there was a trend for the presence of higher levels of IGF-II mRNAs at day 60 of gestation. IGF-I mRNA was not detectable. By in situ hybridization, IGF-II mRNA was localized to non-endocrine cells and to cells lining the blood vessels of the pars distalis, to some presumed endocrine cells in the pars distalis and pars intermedia, and to clusters of cells in the pars nervosa. In contrast, IGF-I and IGF-II peptides were detected in the presumed endocrine cells in the pars distalis and pars intermedia but not in the pars nervosa. Incubation of adenohypophysial cells from term fetuses with IGF-I, but not IGF-II, for 48 h increased specific 125I-Tyr-ovine CRH binding. However, neither IGF-I nor IGF-II had any significant effects on the basal or CRH-stimulated immunoreactive (ir)-ACTH output, the level of POMC mRNA or the number of ir-ACTH positive cells. Infusion of cortisol to fetuses starting at day 96 of gestation for 100 h or at days 120–125 of gestation for 84 h did not affect the level of IGF-II mRNAs in the pars distalis but decreased the levels of POMC mRNA. These results are consistent with IGFs having the potential to influence fetal pituitary function, although probably on cell types other than the corticotrophs. The likely sources of IGFs may be predominantly local (IGF-II) or from extrapituitary sources (IGF-I).

2003 ◽  
Vol 178 (1) ◽  
pp. 71-82 ◽  
Author(s):  
J Honda ◽  
Y Manabe ◽  
R Matsumura ◽  
S Takeuchi ◽  
S Takahashi

IGF-I is expressed in somatotrophs, and IGF-I receptors are expressed in most somatotrophs and some corticotrophs in the mouse pituitary gland. Our recent study demonstrated that IGF-I stimulates the proliferation of corticotrophs in the mouse pituitary. These results suggested that somatotrophs regulate corticotrophic functions as well as somatotrophic functions by the mediation of IGF-I molecules. The present study aimed to clarify factors regulating pituitary IGF-I expression and also the roles exerted by IGF-I within the mouse anterior pituitary gland. Mouse anterior pituitary cells were isolated and cultured under serum-free conditions. GH (0.5 or 1 microg/ml), ACTH (10(-8) or 10(-7) M), GH-releasing hormone (GHRH; 10(-8) or 10(-7) M), dexamethasone (DEX; 10(-8) or 10(-7) M) and estradiol-17beta (e2; 10(-11) or 10(-9) M) were given for 24 h. IGF-I mRNA levels were measured using competitive RT-PCR, and GH and pro-opiomelanocortin (POMC) mRNA levels were measured using Northern blotting analysis. GH treatment significantly increased IGF-I mRNA levels (1.5- or 2.1-fold). ACTH treatment did not alter GH and IGF-I mRNA levels. IGF-I treatment decreased GH mRNA levels (0.7- or 0.5-fold), but increased POMC mRNA levels (1.8-fold). GH treatment (4 or 8 microg/ml) for 4 days increased POMC mRNA levels. GHRH treatment increased GH mRNA levels (1.3-fold), but not IGF-I mRNA levels. DEX treatment significantly decreased IGF-I mRNA levels (0.8-fold). e2 treatment did not affect IGF-I mRNA levels. GH receptor mRNA, probably with GH-binding protein mRNA, was detected in somatotrophs, and some mammotrophs and gonadotrophs by in situ hybridization using GH receptor cDNA as a probe. These results suggested that IGF-I expression in somatotrophs is regulated by pituitary GH, and that IGF-I suppresses GH expression and stimulates POMC expression at the transcription level. Pituitary IGF-I produced in somatotrophs is probably involved in the regulation of somatotroph and corticotroph functions.


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.


1996 ◽  
Vol 271 (4) ◽  
pp. E678-E685 ◽  
Author(s):  
J. Murotsuki ◽  
R. Gagnon ◽  
S. G. Matthews ◽  
J. R. Challis

To test the hypothesis that long-term hypoxemia causes premature activation of the fetal pituitary-adrenal function, we embolized the fetal side of the placenta in pregnant sheep and examined the changes in concentrations of immunoreactive adrenocorticotropic hormone (irACTH), cortisol, and prostaglandin E2 (PGE2) in fetal plasma, and levels and localization of proopiomelanocortin (POMC) mRNA in the pars distalis and the pars intermedia of the fetal pituitary. Twelve fetal sheep were studied (6 embolized and 6 control) for 21 days between 0.74 and 0.88 of gestation. Daily injections of nonradiolabeled microspheres were given into the fetal abdominal aorta to decrease fetal arterial oxygen content by 40-50% of the preembolization values. In the embolized group, concentrations of irACTH, PGE2, and cortisol in fetal plasma increased gradually and were significantly (P < 0.05) elevated above those of controls after day 10, day 16, and day 20, respectively. POMC mRNA levels in the pars distalis of the fetal pituitary were not different from those of controls but were significantly reduced in the pars intermedia (P < 0.05). We conclude that levels of POMC mRNA in the pars distalis are unchanged during long-term hypoxemia possibly because of negative feedback effects of elevated cortisol on the pituitary gland. During long-term fetal hypoxemia, there is a differential regulation of POMC mRNA expression in the pars distalis and pars intermedia.


1981 ◽  
Vol 89 (2) ◽  
pp. 181-186 ◽  
Author(s):  
ALAIN CHATELAIN ◽  
J. P. DUPOUY

The concentration of ACTH in the pars distalis and pars intermedia of the fetal rat hypophysis from days 17–21 of pregnancy was measured with a specific radioimmunoassay and a bioassay using isolated adrenal cells from adult rats. In both lobes of the pituitary gland, a significant correlation was observed between immunoreactive and bioreactive values, expressed as pg equivalents synthetic human 1–39 ACTH per μg protein. In the pars distalis, ACTH concentrations increased steadily from days 17–20 and then remained unchanged to term. At this time they were tenfold higher than on day 17. In the neurointermediate lobe, ACTH was detected only from day 18; the concentration of ACTH increasing between days 18 and 19. At each of the stages of pregnancy examined, the concentration of ACTH in the pars distalis was greater than that in the pars intermedia. These data have demonstrated that ACTH is present in both anterior and neurointermediate lobes of the fetal rat hypophysis, that the functional differentiation of the pars distalis takes place earlier than that of the pars intermedia, and that the concentrations of corticotrophin in the pars distalis and in the pars intermedia have different patterns of development as gestation progresses.


1988 ◽  
Vol 119 (1) ◽  
pp. 16-20 ◽  
Author(s):  
P. J. Coates ◽  
I. Doniach

Abstract. The development of the folliculo-stellate cell in human fetal pituitaries has been investigated by immunocytochemical methods for S-100 protein and glial fibrillary acid protein. S-100 positivity was first observed in pars intermedia cells in a 13-week fetus. Staining with this antiserum is seen in cells of the pars distalis after 15 weeks. Glial fibrillary acid protein was not apparent until 18 weeks, when only cells in the pars intermedia were stained. These cells were not seen in the pars distalis before 28 weeks' gestation, but were present in a 39-week specimen and in a 5 day old baby. In most pituitaries examined, cells staining for S-100 and glial fibrillary acid protein were more concentrated in the pars intermedia than the pars distalis. These results suggest that folliculo-stellate cells in the human pituitary originate in the neurally associated facet of the pars intermedia and pass through this lobe to reach the pars distalis. Since these cells stain for glial related antigens, they may be a modified form of glial cell and arise in the neuroectoderm. Evidence for this hypothesis is given by a lack of both S-100 and glial fibrillary acid protein in the pituitaries of three anencephalic pituitaries. Differences in the timing of S-100 and glial fibrillary acid protein immunoreactivity may be related to either developmental aspects of the folliculo-stellate cell, or to the presence of two distinct cell types.


1975 ◽  
Vol 32 (1) ◽  
pp. 11-19 ◽  
Author(s):  
J. R. McBride ◽  
A. P. van Overbeeke

Adult male sockeye salmon in the final stage of sexual maturation were treated with thiourea for periods of 7–14 wk. The treatment produced strong histological thyroid stimulation but no visible effect on spermatogenesis or development of secondary sexual characteristics. The drug did not affect the interrenal hypertrophy that commonly occurs in these salmon, but slightly inhibited the increase in thickness of the skin. Thiourea induced changes in the pars distalis of the pituitary gland, involving several cell-types, including retardation of gonadotrop development.In gonadectomized fish, thiourea affected neither the skin, nor the interrenal tissue. It caused a marked increase in the height of the thyroid epithelium, correlated with hypertrophy, degranulation, and some vacuolization of PAS-positive cells in the dorso-caudal area of the proximal pars distalis of the pituitary gland. Therefore, these last cells are considered thyrotrops.


Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4435-4451 ◽  
Author(s):  
Burcu Guner ◽  
A. Tuba Ozacar ◽  
Jeanne E. Thomas ◽  
Rolf O. Karlstrom

The vertebrate adenohypophysis forms as a placode at the anterior margin of the neural plate, requiring both hedgehog (Hh) and fibroblast growth factor (Fgf) mediated cell-cell signaling for induction and survival of endocrine cell types. Using small molecule inhibitors to modulate signaling levels during zebrafish development we show that graded Hh and Fgf signaling independently help establish the two subdomains of the adenohypophysis, the anteriorly located pars distalis (PD) and the posterior pars intermedia (PI). High levels of Hh signaling are required for formation of the PD and differentiation of anterior endocrine cell types, whereas lower levels of Hh signaling are required for formation of the PI and differentiation of posterior endocrine cell types. In contrast, high Fgf signaling levels are required for formation of the PI and posterior endocrine cell differentiation, whereas anterior regions require lower levels of Fgf signaling. Based on live observations and marker analyses, we show that the PD forms first at the midline closest to the central nervous system source of Sonic hedgehog. In contrast the PI appears to form from more lateral/posterior cells close to a central nervous system source of Fgf3. Together our data show that graded Hh and Fgf signaling independently direct induction of the PD and PI and help establish endocrine cell fates along the anterior/posterior axis of the zebrafish adenohypophysis. These data suggest that there are distinct origins and signaling requirements for the PD and PI.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Okuma ◽  
Tomoaki Aoki ◽  
Santiago J. Miyara ◽  
Kei Hayashida ◽  
Mitsuaki Nishikimi ◽  
...  

AbstractThe pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = −0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.


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