Loss of Inhibin Advances Follicle Activation and Female Puberty Onset but Blocks Oocyte Maturation in Zebrafish

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Huijie Lu ◽  
Cheng Zhao ◽  
Bo Zhu ◽  
Zhiwei Zhang ◽  
Wei Ge
Keyword(s):  
Oocyte Maturation ◽  
Tumor Formation ◽  
Α Subunit ◽  
Mature Adults ◽  
Sporadic Tumor ◽  
Physiological Importance ◽  
Normal Spermatogenesis ◽  
Puberty Onset ◽  
Female Mutant ◽  
Follicle Activation

Abstract Inhibin was first characterized in mammals as a gonadal dimeric protein that inhibited pituitary follicle-stimulating hormone (FSH) secretion. As in mammals, the inhibin-specific α subunit (INHA/Inha/inha) has also been characterized in teleosts; however, its functions and physiological importance in fish reproduction remain unknown. Using CRISPR/Cas9 method, we generated an inha-deficient zebrafish line and analyzed its reproductive performance. As expected, pituitary expression of fshb increased significantly in both the young and the adult inha mutant. The expression of lhb also increased in the mutant, but only in sexually mature adults. Interestingly, the expression of activin βA (inhbaa) increased significantly in both the ovary and the testis of inha mutant, and the expression of ovarian aromatase (cyp19a1a) also increased dramatically in the mutant ovary. The juvenile female mutant showed clear signs of early follicle activation or precocious puberty onset. However, the adult female mutant was infertile with follicles arrested at the full-grown stage without final oocyte maturation and ovulation. Although follicle growth was normal overall in the mutant, the size and distribution of yolk granules in oocytes were distinct and some follicles showed granulosa cell hypertrophy. In contrast to females, inha-null males showed normal spermatogenesis and fertility. As reported in mammals, we also found sporadic tumor formation in inha mutants. Taken together, our study not only confirmed some conserved roles of inhibin across vertebrates, such as inhibition of FSH biosynthesis and tumor formation, but also revealed novel aspects of inhibin functions such as disruption of folliculogenesis and female infertility but no obvious involvement in spermatogenesis in fish.

Cellular alterations in pituitary tumors

1994 ◽  
Vol 130 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Anna Spada ◽  
Lucia Vallar ◽  
Giovanni Faglia
Keyword(s):  
Transcriptional Activation ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Tumor Formation ◽  
Chromosome 1 ◽  
Ras Gene ◽  
Α Subunit ◽  
Activating Mutations ◽  
Almost All ◽  
Cellular Alterations

Spada A, Vallar L, Faglia G. Cellular alterations in pituitary tumors. Eur J Endocrinol 1994;130:43–52. ISSN 0804–4643 In the last few years, molecular studies on pituitary adenomas have yielded evidence supporting a primary pituitary origin of these tumors. Although the existence of genomic alterations in tumoral cells is strongly suggested by the fact that almost all pituitary adenomas are monoclonal in origin, structural genetic abnormalities such as rearrangement, deletion or mutation, which could result in transcriptional activation, have been identified in a minority of tumors. As far as the possible loss of anti-oncogenes in pituitary tumors is concerned, gene alterations have not been found in the p53 nor in the retinoblastoma gene, while loss of chromosome 1 1q13 sequences, which contain the deduced location of the yet uncloned MEN-1 gene, has been reported in a subset of GH-secreting adenomas. With regard to the activation of dominant oncogenes in the process of tumor formation, activating mutations of either the Gs α-subunit or the ras gene have been identified in a large proportion of GH-secreting adenomas and in individual particularly invasive tumours, respectively. Promoting agents such as hypothalamic neurohormones and growth factors may be required for the selective growth of genetically altered cells. In this respect, it is worth noting that receptor/postreceptor alterations occurring in pituitary tumors may cause an increased action of stimulatory neurohormones with growth promoting properties as well as defective action of inhibitory inputs. Anna Spada, Institute of Endocrine Sciences, Pad. Granelli Ospedale Maggiore IRCCS, via F Sforza 35, Milano 20122, Italy

Immunisation against inhibin enhances follicular development, oocyte maturation and superovulatory response in water buffaloes

2011 ◽  
Vol 23 (6) ◽  
pp. 788 ◽  
Author(s):  
D. R. Li ◽  
G. S. Qin ◽  
Y. M. Wei ◽  
F. H. Lu ◽  
Q. S. Huang ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Plasma Concentrations ◽  
Follicular Development ◽  
Oocyte Quality ◽  
Control Group ◽  
High Group ◽  
Α Subunit ◽  
And Control

This study was carried out to test the feasibility of enhancing embryo production in vivo and in vitro by immunoneutralisation against inhibin or follistatin. In Experiment 1, multi-parity buffaloes were assigned into three groups: High group (n = 8), which received one primary (2 mg) and two booster (1 mg) vaccinations (28-day intervals) with a recombinant inhibin α subunit in 1 mL of white oil adjuvant; Low group (n = 8), which received half that dose; and Control group (n = 7), which received only adjuvant. Immunisation against inhibin stimulated development of ovarian follicles. Following superovulation and artificial insemination, inhibin-immunised buffaloes had more developing follicles than the Control buffaloes. The average number of embryos and unfertilised ova (4.5 ± 0.6, n = 6) in the High group was higher (P < 0.05) than in the Control group (2.8 ± 0.6, n = 5) and was intermediate (4.1 ± 0.7, n = 7) in the Low group. The pooled number of transferable embryos of the High and Low groups (3.2 ± 0.5, n = 13) was also higher (P < 0.05) than that (1.6 ± 0.7, n = 5) of the controls. The immunised groups also had higher plasma concentrations of activin, oestradiol and progesterone. In Experiment 2, the addition of anti-inhibin or anti-follistatin antibodies into buffalo oocyte IVM maturation medium significantly improved oocyte maturation and cleavage rates following parthenogenic activation. Treatment with anti-follistatin antibody also doubled the blastocyst yield from activated embryos. These results demonstrated that immunisation against inhibin stimulated follicular development, enhanced oocyte quality and maturation competence, yielded more and better embryos both in vivo and in vitro.

Molecular Determinants of BK Channel Functional Diversity and Functioning

2017 ◽  
Vol 97 (1) ◽  
pp. 39-87 ◽  
Author(s):  
Ramon Latorre ◽  
Karen Castillo ◽  
Willy Carrasquel-Ursulaez ◽  
Romina V. Sepulveda ◽  
Fernando Gonzalez-Nilo ◽  
...  
Keyword(s):  
Binding Sites ◽  
Muscle Tone ◽  
Gene Diversity ◽  
Single Gene ◽  
Bk Channels ◽  
Bk Channel ◽  
Voltage Sensor ◽  
Channel Structure ◽  
Α Subunit ◽  
Physiological Importance

Large-conductance Ca2+- and voltage-activated K+ (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene ( Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca2+ binding sites) communicate with the pore gates allosterically. In this regard, we review in detail the allosteric models proposed to explain channel activation and how the models are related to channel structure. Considering their extremely large conductance and unique selectivity to K+, we also offer an account of how these two apparently paradoxical characteristics can be understood consistently in unison, and what we have learned about the conduction system and the activation gates using ions, blockers, and toxins. Attention is paid here to the molecular nature of the voltage sensor and the Ca2+ binding sites that are located in a gating ring of known crystal structure and constituted by four COOH termini. Despite the fact that BK channels are coded by a single gene, diversity is obtained by means of alternative splicing and modulatory β and γ subunits. We finish this review by describing how the association of the α subunit with β or with γ subunits can change the BK channel phenotype and pharmacology.

scholarly journals Oocyte Maturation in Starfish

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 476
Author(s):  
Kazuyoshi Chiba
Keyword(s):  
Plasma Membrane ◽  
Oocyte Maturation ◽  
Binding Protein ◽  
Germinal Vesicle ◽  
Phosphatidylinositol 3 Kinase ◽  
Gtp Binding Protein ◽  
Germinal Vesicle Breakdown ◽  
Α Subunit ◽  
Gtp Binding ◽  
Dependent Protein

Oocyte maturation is a process that occurs in the ovaries, where an immature oocyte resumes meiosis to attain competence for normal fertilization after ovulation/spawning. In starfish, the hormone 1-methyladenine binds to an unidentified receptor on the plasma membrane of oocytes, inducing a conformational change in the heterotrimeric GTP-binding protein α-subunit (Gα), so that the α-subunit binds GTP in exchange of GDP on the plasma membrane. The GTP-binding protein βγ-subunit (Gβγ) is released from Gα, and the released Gβγ activates phosphatidylinositol-3 kinase (PI3K), followed by the target of rapamycin kinase complex2 (TORC2) and 3-phosphoinositide-dependent protein kinase 1 (PDK1)-dependent phosphorylation of serum- and glucocorticoid-regulated kinase (SGK) of ovarian oocytes. Thereafter, SGK activates Na+/H+ exchanger (NHE) to increase the intracellular pH (pHi) from ~6.7 to ~6.9. Moreover, SGK phosphorylates Cdc25 and Myt1, thereby inducing the de-phosphorylation and activation of cyclin B–Cdk1, causing germinal vesicle breakdown (GVBD). Both pHi increase and GVBD are required for spindle assembly at metaphase I, followed by MI arrest at pHi 6.9 until spawning. Due to MI arrest or SGK-dependent pHi control, spawned oocytes can be fertilized normally

scholarly journals Paneth cell–derived growth factors support tumorigenesis in the small intestine

2020 ◽  
Vol 4 (3) ◽  
pp. e202000934
Author(s):  
Qing Chen ◽  
Kohei Suzuki ◽  
Luis Sifuentes-Dominguez ◽  
Naoteru Miyata ◽  
Jie Song ◽  
...  
Keyword(s):  
Small Intestine ◽  
Growth Factors ◽  
Small Bowel ◽  
Genetic Model ◽  
Paneth Cell ◽  
Tumor Formation ◽  
Intestinal Epithelial ◽  
Α Subunit ◽  
Conditional Expression ◽  
Small Intestinal

Paneth cells (PCs) are small intestinal epithelial cells that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived Wnt secretion is relevant in vivo remains unknown as intestinal epithelial ablation of Wnt does not affect homeostatic proliferation or restitution after irradiation injury. Considering the importance of growth factors in tumor development, we explored here the role of PCs in intestinal carcinogenesis using a genetic model of PC depletion through conditional expression of diphtheria toxin-α subunit. PC depletion in ApcMin mice impaired adenoma development in the small intestine and led to decreased Wnt3 expression in small bowel adenomas. To determine if PC-derived Wnt3 was required for adenoma development, we examined tumor formation after PC-specific ablation of Wnt3. We found that this was sufficient to decrease small intestinal adenoma formation; moreover, organoids derived from these tumors displayed slower growth capacity. Overall, we report that PC-derived Wnt3 is required to sustain early tumorigenesis in the small bowel and identify a clear role for PC-derived Wnt production in intestinal pathology.

Roles of the activin regulatory system in fish reproduction

2000 ◽  
Vol 78 (12) ◽  
pp. 1077-1085 ◽  
Author(s):  
Wei Ge
Keyword(s):  
Oocyte Maturation ◽  
Biological Activities ◽  
Ovarian Follicle ◽  
Mrna Level ◽  
Type I ◽  
Fish Reproduction ◽  
Potent Effect ◽  
Α Subunit ◽  
Final Oocyte Maturation

Activin (βAβA, βAβB, and βBβb) is a dimeric growth factor with diverse biological activities in vertebrate reproduction. Activin exerts its actions by binding to its specific type II and type I receptors. The activity of activin is regulated by follistatin, its binding protein, and the antagonists inhibin and antivin. All major components of the activin-inhibin-follistatin system have been identified in fish except the α subunit of inhibin. Using goldfish as a model, we have demonstrated that activin is expressed in the pituitary and the recombinant goldfish activin B has novel inverse effects on the expression of GTH β subunits. Activin increases the mRNA level of GTH-Iβ while significantly suppressing the expression of GTH-IIβ. We have also demonstrated the expression of activin and its receptors in the goldfish and zebrafish ovary. Using an in vitro ovarian follicle incubation as the system, we have investigated the involvement of the activin system in the process of final oocyte maturation. Our evidence clearly indicates that activin has potent effect of promoting final oocyte maturation, and that it may play a role in mediating the stimulatory effect of pituitary gonadotropin in the event of oocyte maturation. Key words: activin, inhibin, follistatin, fish, reproduction.

Sign in / Sign up

Export Citation Format

Share Document