The beta-thymosins are a family of related peptides, initially isolated from calf thymus but known to be present in a wide
variety of mammalian and other vertebrate cells and tissues. Thymosin-beta-4 was the first member of the family to
be characterized. Although TMSB4 was initially proposed to be a thymic hormone acting at early stages of T-cell maturation,
the high concentration of the protein and its mRNA in a number of other tissues and cells, as well as the lack of an
identifiable secretory signal sequence, suggested that it had a general function in many cell types. This was confirmed by the
demonstration that TMSB4 forms a 1:1 complex with G-actin in blood platelets and other evidence that it is the only known
G-actin-sequestering protein present at high enough levels in blood platelets to account for the high levels of G-actin in those
cells. Thymosin-beta-10 is closely related in sequence to TMSB4 and is also an actin-sequestering protein.
Hippo ?
General function
Intracellular signaling cascade
Comment
Cellular localization
Secreted, Cytoplasmic, Cytoskeleton
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Hall AK et al reported that administration of pregnant mare's serum gonadotropin (PMSG) to
immature rats provoked a pronounced stimulation of ovarian thymosin beta-10 expression, the maximal effect (2- to 4-fold)
of which coincided with the time at which folliculogenesis was also maximally enhanced. In contrast, the transcriptional
status of the thymosin beta-4 gene varied little in response to the PMSG. Administration of human chorionic gonadotropin
(hCG) to PMSG-primed rats inhibited ovarian thymosin beta-10 but stimulated thymosin beta-4 gene expression.
Gene whose expression is detected by cDNA array hybridization: stress response, cell/cell communication. Also, relative transcript level reproducibly decreases during IVM Rozenn Dalbi?Tran and Pascal Mermilloda
Expression regulated by
FSH, LH
Comment
Hall AK et al reported that thymosin beta 10
mRNA was constitutively expressed as a single abundant transcript in the immature rat ovary.
Administration of PMSG to immature rats resulted in a gradual increase in steady state ovarian
thymosin beta 10 mRNA content detectable as early as 12 h and maximal (2-to 3-fold stimulation above preinjection levels)
48 h after PMSG treatment. Ovarian thymosin beta 10 mRNA levels declined thereafter. In separate experiments treatment of
PMSG (50 IU)-primed rats with hCG (25 IU) precipitated a dramatic (80%) inhibition of ambient ovarian thymosin beta 10
protein and thymosin beta 10 mRNA. HPLC analysis also indicated the presence in the ovary of thymosin beta 4, a variant member of
the same protein family; in general, ovarian thymosin beta 4 levels fluctuated in a manner reciprocal to that exhibited by
thymosin beta 10. A luteolytic dose of prostaglandin F2 alpha (500 micrograms/rat) had little impact on ovarian thymosin
beta 10 gene expression.
Ovarian localization
Oocyte, Granulosa, Luteal cells
Comment
Thymosins ?4 and ?10 are expressed in bovine ovarian follicles and upregulated in cumulus cells during meiotic maturation. Salhab M et al. ?Thymosins are small proteins that regulate the actin cytoskeleton and are involved in cell motility, differentiation, the induction of metalloproteinases, in anti-inflammatory processes and tumourigenesis. However, their roles in the ovary have not yet been elucidated. Using transcriptomics and real time reverse transcription-polymerase chain reaction validation, the present study demonstrates that thymosin ?4 (TMSB4) and thymosin ?10 (TMSB10) are upregulated in bovine cumulus cells (CCs) during in vitro maturation of cumulus-oocyte complexes (COCs) in parallel with an increase in mRNA expression of HAS2, COX2 and PGR genes. Using immunocytochemistry, both proteins were found to be localised mainly in granulosa cells, CCs and oocytes, in both the cytoplasm and nucleus, as well as being colocalised with F-actin stress fibres in CCs. Using different maturation mediums, we showed that the expression of TMSB10, but not TMSB4, was positively correlated with COC expansion and progesterone secretion and negatively correlated with apoptosis. Immunofluorescence, coupled with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL), demonstrated the absence of TMSB4 and/or TMSB10 in apoptotic cells. TMSB10 expression was higher in COCs matured in vivo than in vitro, and differences related to the age of the animal were observed. TMSB4 and/or TMSB10 expression was unchanged, whereas HAS2 overexpressed in CCs from oocytes that developed to the blastocyst stage in vitro compared with those that did not. Thus, TMSB4 and/or TMSB10 ovarian expression patterns suggest that these two thymosins may be involved in cumulus modifications during maturation.