Castration induces up-regulation of intratumoral androgen biosynthesis and androgen receptor expression in an orthotopic VCaP human prostate cancer xenograft model.

Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration).

Peritubular myoid cells have a role in postnatal testicular growth.

FSH stimulates testicular growth by increasing Sertoli cell proliferation and elongation of seminiferous cords. Little is known about the peritubular myoid cells in testicular development. In order to investigate the role of peritubular myoid cells in early testicular growth in rodents, two traditional models to induce testicular growth were used: FSH treatment and hemicastration.

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats.

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec®). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment.

Increased exposure to estrogens disturbs maturation, steroidogenesis, and cholesterol homeostasis via estrogen receptor alpha in adult mouse Leydig cells.

Deteriorated male reproductive health has been connected to overexposure to estrogens or to imbalanced androgen-estrogen ratio. Transgenic male mice expressing human aromatase (AROM(+) mice) serve as an apt model for the study of the consequences of an altered androgen-estrogen ratio. Our previous studies with AROM(+) mice showed that low androgen levels together with high estrogen levels result in cryptorchidism and infertility.

Functional in vitro model to examine cancer therapy cytotoxicity in maturing rat testis.

Childhood cancer treatment can lead to infertility. Organ culture of early postnatal testicular tissue might provide a valuable approach to the study of acute testicular toxicity. The aim of the present study was to develop a functional in vitro organ culture method, in order to identify sensitive target cells to doxorubicin-induced cytotoxicity in immature rat testis during germ cell migration prior initiation of the first wave of spermatogenesis.

Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis.

Imatinib mesylate (Glivec, STI 571; Novartis), a small-molecular analog of ATP that potently inhibits the tyrosine kinase activities of Bcr-Abl, PDGFR-alpha, PDGFR-beta, c-Fms, Arg and c-kit, is one of the novel molecularly targeted agents being introduced into cancer therapy. Stem cell factor (SCF)/c-kit and platelet-derived growth factor (PDGF) signaling pathways regulate postnatal formation of the pools of spermatogonial stem cells and Leydig cells in the rat testis. The effect of short postnatal imatinib exposure on fertility of the male rats and offspring of these animals were investigated.

Tissue-specific expression of aryl hydrocarbon receptor and putative developmental regulatory modules in Baltic salmon yolk-sac fry.

The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration.