scholarly journals Deficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity

Reproduction ◽  
2007 ◽  
Vol 133 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Jiyoung Hong ◽  
Sung Tae Kim ◽  
Susanne Tranguch ◽  
David F Smith ◽  
Sudhansu K Dey

FKBP52 is a member of the FK506-binding family of immunophilins and serves as a co-chaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Male mice missingFkbp52are infertile, and this infertility has been ascribed to compromised sensitivity of the anterior prostate, external genitalia, and other accessory sex organs to androgen. Here, we show additional defects contributing to infertility. We found that epididymalFkbp52−/−sperm are sparse often with aberrant morphology, and they have reduced fertilizing capacity. This phenotype, initially observed in null males on a C57BL/6/129 background, is also maintained on a CD1 background. Expression studies show that while FKBP52 and androgen receptor are co-expressed in similar cell types in the epididymis, FKBP52 is also present in epididymal sperm flagella. Collectively, our results suggest that reduced number and abnormal morphology contribute to compromised fertilizing capacity ofFkbp52−/−sperm. This study is clinically relevant because unraveling the role of immunophilin signaling in male fertility will help identify new targets for male contraceptives and/or alleviate male infertility.

1992 ◽  
Vol 40 (5) ◽  
pp. 533 ◽  
Author(s):  
PH Krutzsch ◽  
RA Young ◽  
EG Crichton

The anatomy and chronology of reproductive events in male and female Rhinolophus megaphyllus from eastern Australia (27-32-degrees-S.) is discussed. Rhinolophus megaphyllus was monoestrous and monotocous. A delay of several months occurs between the delivery of spermatozoa to the caudae epididymides (late summer/early autumn) and copulation/ovulation/conception (winter), which occur towards the termination of the spermatogenic cycle. There is no storage of sperm in female tracts prior to ovulation but epididymal sperm storage persists beyond the time of birth (late spring). Male, but not female, readiness to initiate reproduction prior to the onset of winter, places this species in an 'intermediate' position with features of both temperate and tropical chiropteran reproductive cycle patterns. The presence of an extroverted corpus luteum in the female and of a complement of accessory sex organs in the male are normal glandular features for members of this chiropteran family. The role of the urethral gland is unknown; however, since there is no vaginal plug, its products apparently do not coagulate in the vagina in this species following insemination.


Steroids ◽  
1991 ◽  
Vol 56 (2) ◽  
pp. 66-71 ◽  
Author(s):  
Jaime Steinsapir ◽  
Thomas G. Muldoon

2001 ◽  
Vol 13 (8) ◽  
pp. 673 ◽  
Author(s):  
Jean D. Wilson

A role for 5α-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5α-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5α-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a Δ4, 3-keto configuration. 5α-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone–receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5α-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.


2020 ◽  
Vol 21 (18) ◽  
pp. 6573 ◽  
Author(s):  
Federica Saponaro ◽  
Alessandro Saba ◽  
Riccardo Zucchi

Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.


1999 ◽  
Vol 253 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Charlotte Bevan ◽  
Malcolm Parker

Author(s):  
W.T. Gunning ◽  
M.R. Marino ◽  
M.S. Babcock ◽  
G.D. Stoner

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.


Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.


1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.


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