Cathepsins are papain family cysteine
proteinases involved in a variety of physiologic. Faust, P. L et al reported the cloning and sequence analysis of cDNA for human cathepsin D.
NCBI Summary:
This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Cellular localization
Secreted, Cytoplasmic
Comment
Ovarian function
Follicle atresia, Ovulation, Oocyte maturation
Comment
Cathepsin B activity has a crucial role in the developmental competence of bovine COCs exposed to heat-shock during in vitro maturation. Balboula AZ 2013 et al.
Cathepsin B was found to be correlated inversely with the quality of bovine oocytes and embryos. The aims of this study were to evaluate: 1) the relationship between heat shock during in vitro maturation (IVM) of bovine cumulus oocyte complexes (COCs) and cathepsin B activity in relation to apoptosis, 2) the effect of supplementation of cathepsin B inhibitor (E-64) during heat-shocked IVM on the embryo development. After IVM at 38.5 C for 22 hr (control group) or at 38.5 C for 5 hr followed by 41 C for 17 hr (Heat shock group) either with or without 1 M E-64, activities and protein expressions of cathepsin B and caspase 3 were evaluated as well as TUNEL staining. After IVF, developmental rate, total cell number and percent of apoptotic cells in blastocysts were evaluated on day 8 (day 0 = IVF day). Heat shocked IVM COCs showed significantly high activities and expressions of both cathepsin B and caspase 3 accompanied with a significant increase of TUNEL positive cells. Addition of E-64 significantly decreased the activities of cathepsin B, caspase 3 and TUNEL positive cells in heat-shocked IVM COCs. Moreover, addition of 1 M E-64 during IVM under heat shock condition significantly improved both developmental competence and quality of the produced embryos. These results indicate that heat shock induction of cathepsin B is associated with apoptosis of COCs, and inhibition of cathepsin B activity can improve the developmental competence of heat-shocked COCs during IVM.
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Kainz C, et al. reported the presence of cathepsin D in follicular fluids and discussed its possible role in ovulation.
Expression regulated by
FSH, LH, Steroids
Comment
Dhanasekaran N et al reported that upon stimulation with
FSH or PMSG, the cathepsin-D activity, a representative lysosomal enzyme of granulosa cells, is reduced by 50% . 17 beta-Estradiol was unable to mimic this effect. Dihydrotestosterone (DHT), however,
at a dose of 1 mg/rat was able to inhibit PMSG's tropic action. It brought about an increase in cathepsin-D activity and reduction in steroidogenic activity of isolated granulosa cells. The atretogenic activity of DHT could be relieved by supplementation with exogenous FSH. DHT was observed to significantly reduce endogenous FSH and LH
levels within 12-18 h of its injection suggesting that its atretic effect was due to its action at the pituitary rather than the
gonad.
Ovarian localization
Granulosa, Luteal cells
Comment
Dhanasekaran N et al reported that when
isolated cells from gonadotropin-treated rats were analyzed for the cathepsin-D activity, the granulosa cells of the ovary showed a reduction
in the free as well as in the total lysosomal enzyme activities in response to FSH/PMSG; the stromal and thecal compartment
of the ovary showed a reduction only in the free activity in response to hCG/PMSG.
Lahav M et al reported intracellular distribution of cathepsin D in rat corpora lutea in relation to
reproductive state and the action of prostaglandin F2alpha and prolactin.
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Hradek DI et al reported that cathepsin D levels (per mg tissue) were significantly greater in ovarian follicle and corpus luteum compared with cortex. Although there was not a clear correlation between
enzyme activity in the cortex and day of the menstrual cycle or patient age, levels of enzyme activity appeared to decrease
with each parameter.
Phenotypes
Mutations
1 mutations
Species: ovine
Mutation name: type: naturally occurring fertility: fertile Comment: Genome-wide differential expression profiling of mRNAs and lncRNAs associated with prolificacy in Hu sheep. Feng X et al. (2018) Reproductive ability, especially prolificacy, impacts sheep profitability. Hu sheep, a unique Chinese breed, is recognized for its high prolificacy, early sexual maturity, and year-round estrus. However, little is known about the molecular mechanisms underlying high prolificacy in Hu sheep. To explore the potential mRNAs and long non-coding RNAs (lncRNAs) involved in Hu sheep prolificacy, we performed an ovarian genome-wide analysis of mRNAs and lncRNAs(Kung, 2013 #2) during the follicular stage using Hu sheep of high prolificacy (HP, litter size = 3; three consecutive lambings) and low prolificacy (LP, litter size = 1; three consecutive lambings). Plasma LH concentration was higher in the HP group than in the LP group (P < 0.05) during the follicular stage. Subsequently, 76 differentially expressed mRNAs (DE-mRNAs) and five differentially expressed lncRNAs (DE-lncRNAs) were identified by pairwise comparison; qRT-PCR analysis of 10 randomly selected DE genes (mRNA and lncRNA) were consistent with the sequencing results. Gene Ontology analysis of DE-mRNAs revealed significant enrichment in immune response components, actin filament severingand phagocytosis. Pathway enrichment analysis of DE-mRNAs indicated a predominance of immune function pathways, including phagosomes, lysosomes and antigen processing. We constructed a co-expression network of DE-mRNAs and mRNA-lncRNAs, withC1qA,CD53,CTSB,CTSS,TYROBP, andAIF1as the hub genes. Finally, the expression of lysosomal protease cathepsin genes,CTSBandCTSD,were significantly upregulated in sheep ovaries in the HP group compared to the LP group (P < 0.05). These differential mRNAs and lncRNAs may provide information on the molecular mechanisms underlying sheep prolificacy.//////////////////