PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Inhibin-beta Subunits”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1998

Isolation and characterization of 5'-regulatory region of mouse activin beta A subunit gene.

We isolated genomic clones that contain the 5'-flanking region of the mouse activin beta A subunit gene. The nucleotide sequence determination of the 5'-flanking region of the gene and the comparison of that with the reported mouse cDNA structure identified the putative 5' regulatory region, a novel first exon and a part of the first intron of the gene within this region. The putative 5' regulatory region of the mouse activin beta A subunit gene directed the expression of CAT gene in transfected HT1080 cells. Successive deletions of this region demonstrated a 400-bp region that exerts a strong positive effect on promoter activity of the mouse activin beta A subunit gene.

Animals↗
PubMed2000

Immunoexpression of inhibin alpha subunit, inhibin/activin betaA subunit and CD99 in ovarian tumors.

OBJECTIVE: Anti-inhibin alpha and inhibin/activin betaA subunit and anti-CD99 monoclonal antibodies (mAbs) have recently been demonstrated to be able to label ovarian granulosa cells; thus, they may be of value in the diagnosis of granulosa cell tumors. The present study aimed to determine what combination of these mAbs may be useful for the differential diagnosis of sex cord-stromal tumors of ovary. DESIGN: Immunohistochemical analyses with anti-inhibin alpha and inhibin/activin betaA subunit antibody and anti-CD99 mAb were performed on 42 ovarian tumors, including sex cord-stromal tumors (29), ovarian epithelial cancers (10), and Krukenberg tumors (3). RESULTS: All sex cord-stromal tumors were positive for inhibin alpha subunit, and 17 cases (58.6%) of sex cord-stromal tumors were immunoreactive for inhibin/activin betaA subunit. Epithelial tumors and Krukenberg tumors were all negative for inhibin/activin betaA subunit except mucinous carcinoma, which showed strong cytoplasmic immunoreactivity. All sex cord-stromal tumors except one granulosa cell tumor showed membranous staining for CD99. A case of serous carcinoma and a case of mucinous carcinoma were positive for CD99, and the remaining epithelial tumors and Krukenberg tumor were all negative for CD99. CONCLUSIONS: The results of immunohistochemical analysis, together with literature review, suggest that inhibin alpha subunit may be a useful diagnostic marker for sex cord-stromal tumor of the ovary. In addition, anti-CD99 antibody may be useful for the differential diagnosis between ovarian tumors. Inhibin/activin betaA subunit has a limited usefulness in the differential diagnosis of ovarian tumor because of its wider immunoreactivity for both sex cord-stromal tumors and mucinous carcinomas. The differential diagnosis of sex cord-stromal tumors of the ovary would be better made with a combined use of both anti-inhibin alpha subunit and anti-CD99 mAbs.

12E7 Antigen↗
PubMed1998

Immunolocalization of inhibin and activin subunits in human endometrium across the menstrual cycle.

Inhibin/activin alphaC/alphaN and betaA subunits were localized immunohistochemically in the human endometrium throughout the menstrual cycle using an affinity-purified sheep polyclonal antibody raised against the alphaC/alphaN subunit and an affinity-purified rabbit polyclonal antibody raised against the betaA subunit. The betaB subunit was below the level of detection in all human endometrial samples tested. Immunoreactive inhibin alphaC/alphaN subunit was localized in the luminal epithelium, glandular epithelium, stromal tissues and vascular endothelium with no significant variation across the normal menstrual cycle. Immunoreactive betaA subunit, common to inhibin A and activins AA and AB was localized in the luminal and glandular epithelium and in migratory cells while the endometrial stromal cells, decidua, vascular smooth muscle and endothelium were devoid of immunoreactivity. A significant variation of immunoreactive betaA subunit was observed in glandular and luminal epithelium across the normal menstrual cycle. In proliferative endometrium, only a very low level of betaA immunostaining was seen in luminal and glandular epithelium, while the luminal epithelial staining increased significantly in the early secretory phase and remained relatively constant over the rest of the menstrual cycle. A progressive increase in betaA immunoreactivity was observed also in the glandular epithelium during the secretory phase reaching a maximum in the late secretory phases, and decreasing at menstruation. Co-localization studies on serial sections suggested that the migratory cells expressing strong betaA immunoreactivity were macrophages and neutrophils but not eosinophils or mast cells. Thus, cells within the human endometrium are capable of expressing inhibin/activin molecules in vivo. The variation in the pattern of secretion of the betaA subunit across the menstrual cycle suggests that activin peptides may have a physiological role in endometrial function.

Activins↗
PubMed1996

Human activin betaA gene. Identification of novel 5' exon, functional promoter, and enhancers.

On the basis of cDNA cloning, primer extension, and transfection experiments, we identified a novel 5' exon of the human activin betaA subunit gene, and found its enhancer and promoter regions as well as multiple transcription start sites. A series of deletion and mutation analyses of the enhancer sequences defined the 45-base pair core region (DR-1 core) containing two short elements with similarity to AP-1 (12-O-tetradecanoylphorbol-13-acetate response element; TRE) and CREB/ATF (cyclic AMP response element; CRE) binding sites, both of which were necessary for full enhancer activity. Gel shift and antibody supershift assays using DR-1 core region revealed the formation of two specific DNA-protein complexes, one of which could be partially dissociated by a competing oligonucleotide containing a single copy of the consensus TRE, but the other of which contained neither CREB/ATF nor AP-1 as major components. Although 12-O-tetradecanoylphorbol-13-acetate and cAMP induced the activin enhancer/promoter-driven CAT activity, such drug induction was obscured when either the TRE- or CRE-like elements were mutated in the native promoter context. Our results demonstrate that the promoter and enhancer regions identified here are essential for maintaining the efficient promoter activity of the human activin betaA subunit gene.

Activins↗
PubMed1995

Molecular cloning of cDNA for equine ovarian inhibin/activin beta A subunit.

cDNAs encoding equine inhibin/activin beta A subunit were isolated from an equine follicle cDNA library and characterized. Using primers based on the rat inhibin/activin beta A subunit cDNA sequence, a RT-PCR was performed to generate the probe for screening. Four positive clones were isolated. Analysis of the nucleotide sequence of these clones revealed that two pairs of identical clones were present, Eq-beta A-1 (0.9 kb) and Eq-beta A-2 (1.5 kb). Eq-beta A-2 clone contained a complete open reading frame encoding 426 amino acids. The deduced amino acid sequence of equine inhibin/activin beta A subunit showed high similarity (> 90%) to those of five other mammalian species. Northern blot analysis revealed that placenta from mare on day 180 of pregnancy contained a 1.5 kb inhibin/activin beta A subunit mRNA.

Activins↗
PubMed1998

Inhibins, activins, and follistatins: expression of mRNAs and cellular localization in tissues from men with benign prostatic hyperplasia.

BACKGROUND: The transforming growth factor beta (TGF beta) superfamily of growth factors includes activins and inhibins, which have been shown to be present in the rat ventral prostate, and human prostate tumor cell lines, although their localization in benign prostatic hyperplasia (BPH) tissue is currently unknown. METHODS: BPH tissues were obtained at surgery, and the mRNA expression for the inhibin alpha, beta A, beta B subunits, the putative activin beta C subunit, the activin type II receptor (ActRII), and the activin binding protein, follistatin, was determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analysis. Antibodies specific for alpha, beta A, beta B, activin A, and follistatin were used to determine the localization of these proteins in BPH tissue specimens. RESULTS: Southern blot analysis confirmed that mRNA for ActRII, beta C subunit, and follistatin was present in all biopsy samples assayed. However, alpha, beta A, and beta B subunit mRNA expression was variable between patient samples. Immunohistochemistry demonstrated the predominant localization of beta A, beta B, and activin A proteins to the epithelium of BPH tissues. No immunoreactivity for the inhibin alpha subunit was detected; follistatin immunoreactivity was localized to the fibroblastic stroma. CONCLUSIONS: The compartmentalization of activin subunit proteins to the epithelium, and of follistatin to the stroma, suggests that a paracrine interaction occurs between the activin ligands and follistatin-binding proteins in BPH tissue.

Activin Receptors↗
PubMed1999

Male sterility in transgenic mice expressing activin betaA subunit gene in testis.

Activins and inhibins, which are endocrine regulators of anterior pituitary function, have also been reported to participate in the paracrine and autocrine regulation of reproductive function. To determine the in vivo effects of overexpressed activin/inhibin, we generated transgenic mice carrying the human activin/inhibin betaA subunit mini gene under the regulatory control of the mouse methallothionein promoter. In one of the transgenic line analyzed, the betaA subunit gene was preferentially expressed in the testis. Ectopic and allochronic expression of the betaA gene started at 3 weeks after birth and transgenic male mice became sterile in the ensuing several weeks. Histological analysis revealed testicular degeneration in these mice. The results from this transgenic line strongly support the in vivo activity of activin/inhibin in male reproductive functions.

Animals↗
PubMed1998

Expression and function of activin beta A during mouse cardiac cushion tissue formation.

The formation of cardiac cushion tissue, which ultimately contributes to formation of the valves and septa, is dependent on the regional activation of cardiac endothelial cells to undergo an epithelial-mesenchymal transition. This endothelial transition was correlated with activin betaA mRNA expression by Northern and in situ hybridization in both a temporal and spatial manner in developing mouse embryos. Activin betaA was the only subunit of the inhibin family detected during the initial phase of endothelial cell transition; activin betaB was detected at later stages, and inhibin alpha was not detectable in the heart. An in vitro assay that has been used to study mesenchymal cell formation in chick was modified for use with mammalian embryos. Conditioned media from embryonic mouse cardiocyte cultures was shown to substitute for the endogenous inductive signal in these assays. The presence of activin betaA was demonstrated by Western blot analysis of the cardiocyte conditioned media (CCM). Modified antisense oligonucleotides to activin betaA inhibited the endothelial-mesenchymal transition in the assay system, which was not affected by control oligonucleotides. Adapting the avian culture system for use with mice enabled the use of tissue from mice with a null allele for activin betaA. CCM produced from embryos homozygous for the mutant betaA allele did not contain activin betaA and was used in in vitro assays. CCM lacking activin betaA produced fewer mesenchymal cells from cardiac endothelial monolayers than CCM with activin betaA. Localized expression of activin betaA in the embryonic heart indicates a possible role in the endothelial-mesenchymal transition. Bioassays in which activin betaA expression is blocked or activin betaA is absent from the media indicate that activin betaA promotes the formation of mesenchymal cells in the endothelial cushions, which are required for normal septation.

Alleles↗
PubMed1997

Equine inhibin/activin beta A-subunit mRNA is expressed in the endometrial gland, but not in the trophoblast, during pregnancy.

The expression of both inhibin alpha- and inhibin/activin beta A-subunit mRNA was examined in equine uteroplacental tissues collected during pregnancy (days 90 to 300). Northern blot analysis revealed that 5 transcripts (7.0, 4.1, 3.4, 2.6, 1.5 kb) of beta A-subunit were present, and the most abundantly expressed transcript was the 1.5 kb one. Relatively high levels of the 1.5 kb transcript were seen in the second trimester of pregnancy compared to what was found in the third trimester. To identify the tissue localization of beta A-subunit mRNA, in situ hybridization was performed, and the positive signal was observed exclusively in the endometrial glands, but not in the fetal placental tissue (trophoblast) at days 150, 210, and 300 of pregnancy. On the other hand, inhibin alpha-subunit transcript could not be detected at any stage of pregnancy examined either by Northern blot analysis or in situ hybridization. Although the factor(s) regulating the gene expression of beta A-subunit in this equine tissue is currently unknown, these results suggest that activin, but not inhibin, is predominantly produced in the endometrial glands of the pregnant mare, and thus produced activin may play a paracrine or endocrine role during pregnancy in this species.

Animals↗
PubMed2000

Transient expression of activin betaA mRNA on osteoprogenitor cells in rat bone regeneration after drill-hole injury.

We investigated the expression of activin betaA on osteoprogenitor cells in the regenerating bone and bone marrow of the rat femur after drill-hole injury, by immunocytochemistry and in situ hybridization. The periosteum and endosteum adjacent to the wound region showed marked thickening at day 3 and abundant osteoprogenitor cells, which were immunoreactive for proliferating cell nuclear antigen and showed positive reactions for alkaline phosphatase activity, and existed in the inner layer of the periosteum as well as in the endosteum. During the same period, these osteoprogenitor cells began to exhibit activin betaA immunoreactivity and mRNA expression. However, the latter expression gradually reduced the intensity as the cells started to express osteocalcin mRNA during their differentiation to osteoblasts participating in the periosteal and medullary bone formation from day 5. Immunoreactivity for activin type IB and II receptors was also found on activin betaA-immunoreactive cells between days 3 and 7. The above findings suggest that proliferating osteoprogenitor cells, before their transformation to osteoblasts, transiently produce and release activin A, which may play crucial roles in bone and bone marrow regeneration in a receptor-mediated, autocrine and paracrine fashion.

Animals↗
PubMed2000

Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions.

The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-beta superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-beta superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function.

Activins↗
PubMed2001

In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A.

OBJECTIVE: Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn-omas). Since many of the NFAs and Gn-omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS AND METHODS: Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn-omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)-producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn-omas. RESULTS: Gn-omas were found to secrete significantly more activin A in their culture medium than PRL- and GH-producing adenomas (P < 0.05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0.56, P < 0.005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0.73, P < 0.0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0.79, P < 0.0005). CONCLUSIONS: It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.

Activins↗
PubMed2001

Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome.

Familial polycystic ovarian syndrome (PCOS) has been proposed to be linked to a site near the follistatin gene. We studied the concentrations of circulating follistatin, activin A and inhibin B in well-characterized subjects with PCOS (n = 108) and controls without PCOS (n = 20). Mean (+/- SEM) concentrations of follistatin were higher (P < 0.05) in PCOS (0.27 +/- 0.03 ng/ml) than controls (0.15 +/- 0.02 ng/ml) and activin A were lower (P < 0.05) in PCOS (0.20 +/- 0.01ng/ml) than controls (0.24 +/- 0.02 ng/ml). Inhibin B concentrations were not different between the two groups: PCOS (0.06 +/- 0.01ng/ml), and controls (0.06 +/- 0.01ng/ml). It is proposed that higher concentrations of follistatin with lower concentrations of activin A may relate to follicular development not proceeding beyond 8-10 mm and may be partly responsible for the lack of pre-ovular follicle development in PCOS.

Activins↗
PubMedDate not supplied

Linkage mapping of the ovine alpha-inhibin (INHA) beta(A)-inhibin/activin (INHBA) and beta(B)-inhibin/activin (INHBB) genes.

A full-sib mapping population was typed for Taql Southern blot RFLPs at the ovine alpha-inhibin (INHA), beta(A)-inhibin/activin (INHBA), and beta(B)-inhibin/activin (INHBB) loci. The most likely positions were found by genetic linkage analysis. INHA was placed on ovine chromosome 2q, between microsatellite markers BM6444 and INRA135, while INHBB was located 39 cM proximal to INHA between markers BMS1126 and BMS2626. The INHBA gene, a comparative mapping anchor locus, mapped to chromosome 4, between microsatellites OARCP26 and BMS719. These data confirm and refine previous chromosomal assignments by in situ hybridization, provide comparative mapping information, and identify microsatellite markers suitable for QTL association studies with inhibin/activin genes in ruminants.

Activins↗
PubMed1989

Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism.

Male rats were either unilaterally or bilaterally castrated, or were rendered cryptorchid when they were either 15 or 45 days old. Subsequently, blood was sampled over the next several weeks and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and immunoreactive inhibin-alpha (irI alpha) levels were measured by specific radioimmunoassays (RIAs). At the end of the experiment, gonadal expression of inhibin-alpha, inhibin-beta A, and inhibin-beta B subunits was measured by S1 nuclease analysis and in situ hybridization. In both age groups, bilateral castration (BC) produced the expected marked (p less than or equal to 0.01) increases in plasma LH and FSH levels, and concomitant decreases in T and irI alpha secretion within 1 - 2 days after surgery. In 15-day-old animals, unilateral castration (UC) significantly increased FSH and decreased circulating levels of irI alpha, but did not measurably alter LH or androgen production. At 7 days after surgery, the level of inhibin mRNA in the remaining testis was unchanged. In 45-day-old animals, UC caused a measurable increase in FSH, with little or no changes in the circulating levels of irI alpha. Plasma T levels were lowered (p less than or equal to 0.05) by UC; however, there were no statistical changes in LH levels in these UC rats. Finally, T administration markedly reversed UC-induced increase in FSH secretion in both age groups. Androgen therapy also interfered with inhibin release in 45-day-old, but not in 15-day-old rats. In rats 15 days old at the time of surgery, cryptorchidism produced a small but measurable increase (p less than or equal to 0.05) in LH release at Week 6 only, which was accompanied by a significant (p less than or equal to 0.01) decline in T secretion. Plasma FSH levels were elevated at all times in cryptorchid rats, and at 2, 4, and 6 wk, these levels were not statistically distinguishable (p greater than 0.05) from those of castrated animals. In this group of rats, cryptorchidism caused a transient increase (p less than or equal to 0.05) in irI alpha values 1 wk after surgery, but no changes at later times. Finally, measurement of testicular inhibin-alpha subunit messenger RNA (mRNA) levels showed an approximately 2-fold increase compared to total RNA levels in the testis. However, because of the significant decrease in total RNA levels per testis caused by cryptorchidism, the absolute change in inhibin-alpha subunit mRNA levels per testis corresponded to an approximately 3-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Focal brain injury increases activin betaA mRNA expression in hippocampal neurons.

The role of activin in the mammalian brain is of increasing interest as evidence accumulates to suggest a number of different neural functions. Here, we report that activin betaA mRNA is transiently induced in dentate gyrus neurons after unilateral mechanical brain injury by saline injection. Expression is dependent on NMDA receptor activation since pretreatment with MK801 (5 mg/kg, i.p.) largely attenuates the signal. Induction also requires de novo protein synthesis, as cycloheximide (10 mg/kg, i.p.) pretreatment abolishes the expression of activin betaA mRNA 1 h after injury. These results show that activin betaA mRNA expression is regulated by excitatory activity induced by focal brain injury and suggests a possible neuroplastic role in the recovery from such injury.

Animals↗
PubMed1998

Activin is an essential early mesenchymal signal in tooth development that is required for patterning of the murine dentition.

Development of the mammalian tooth has been intensively studied as a model system for epithelial/mesenchymal interactions during organogenesis, and progress has been made in identifying key molecules involved in this signaling. We show that activin betaA is expressed in presumptive tooth-germ mesenchyme and is thus a candidate for a signaling molecule in tooth development. Analysis of tooth development in activin betaA mutant embryos shows that incisor and mandibular molar teeth fail to develop beyond the bud stage. Activin betaA is thus an essential component of tooth development. Development of maxillary molars, however, is unaffected in the mutants. Using tissue recombination experiments we show that activin is required in the mesenchyme prior to bud formation and that although activin signaling from mesenchyme to epithelium takes place, mutant epithelium retains its ability to support tooth development. Implantation of beads soaked in activin A, into developing mandibles, is able to completely rescue tooth development from E11.5, but not E12.5 or E13.5, confirming that activin is an early, essential mesenchyme signal required before tooth bud formation. Normal development of maxillary molars in the absence of activin shows a position specific role for this pathway in development of dentition. Functional redundancy with activin B or other TGFbeta family members that bind to activin receptors cannot explain development of maxillary molars in the mutants since the activin-signaling pathway appears not to be active in these tooth germs. The early requirement for activin signaling in the mesenchyme in incisor and mandibular molar tooth germs must be carried-out in maxillary molar mesenchyme by other independent signaling pathways.

Activins↗