INVESTIGATION OF THE ROLE OF P97/VCP IN AUTOPHAGIC DEGRADATION OF ANDROGEN-BINDING PROTEIN IN SERTOLI CELLS

16th National 2 nd International Congressof Histology and Embryology, Sakarya, Turkey, 26 - 28 September 2024, pp.81, (Summary Text)

Background: Androgen-binding protein (ABP) is a protein produced by Sertoli cells that

directly influences sperm production by ensuring androgen binding in the testicular tubules.

Irregularities in the production, degradation, and release of ABP are associated with a number

of endocrine and andrological disorders of the male reproductive system. ABP metabolism in

Sertoli cells is largely unknown. Recent studies have shown that autophagy in rat Sertoli cells

is regulated by testosterone, which prolongs the biological half-life of ABP. p97/Valosin-

containing protein (VCP) is a chaperone protein that belongs to the ATPase family and plays a

role in a variety of cellular processes, including regulation of the cell cycle, ER-associated

degradation (ERAD), autophagy, apoptosis, and the ubiquitin-proteasome system (UPS).

Regarding its role in autophagy, its absence impairs both the formation and maturation of

autophagosomes, resulting in impaired autophagy. However, the relationship of p97/VCP with

the autophagic degradation of ABP is unknown.

Aim: Our study aims to determine whether p97/VCP has a relationship with ABP in the

mouse Sertoli cell line. Our hypothesis is that p97/VCP is involved in the autophagic

degradation of ABP in mouse Sertoli cells.

Material and methods: Expression of ABP and p97/VCP in the mouse Sertoli cell line (15P-1)

in the presence of autophagy activator, inhibitor, and testosterone was determined by

immunocytochemistry and western blot methods. The co-localization of ABP and p97/VCP

was investigated by a double immunofluorescence method. The p97/VCP gene expression

was suppressed by p97/VCP siRNAs, and siRNA transfection methods were used to

determine whether ABP was affected by this suppression.

Results: A decrease in VCP, ABP, LC3B, and p62 proteins was observed in the groups

suppressed with VCPsi and receiving QC+T (p<0.05). This revealed for the first time in the

literature the association between ABP and p97/VCP, which is related to male reproductive

health and directly affects sperm production, and provided the first information on the

importance of p97/VCP in ABP-related endocrine and andrologic diseases.

Conclusion: Finally, it will form the basis for studies in various tissues such as the brain, liver,

and placenta, where ABP is expressed outside the testis and p97/VCP expressions will be

linked to ABP-dependent pathologies in these tissues.

Keywords: ABP, Autophagy, Testosterone, p97/VCP, Sertoli cell line 15P-1