scholarly journals Tetrapeptides Modelled to the Androgen Binding Site of ZIP9 Stimulate Expression of Tight Junction Proteins and Tight Junction Formation in Sertoli Cells

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 55
Author(s):  
Marie-Louise Möller ◽  
Ahmed Bulldan ◽  
Georgios Scheiner-Bobis

Androgens stimulate the expression of tight junction (TJ) proteins and the formation of the blood–testis barrier (BTB). Interactions of testosterone with the zinc transporter ZIP9 stimulate the expression of TJ-forming proteins and promote TJ formation in Sertoli cells. In order to investigate androgenic effects mediated by ZIP9 but not by the nuclear androgen receptor (AR), the effects of three tetrapeptides fitting the androgen binding site of ZIP9 were compared with those induced by testosterone in a Sertoli cell line expressing ZIP9 but not the AR. Three tetrapeptides and testosterone displaced testosterone-BSA-FITC from the surface of 93RS2 cells and stimulated the non-classical testosterone signaling pathway that includes the activation of Erk1/2 kinases and transcription factors CREB and ATF-1. The expression of the TJ-associated proteins ZO-1 and claudin-5 was triggered as was the re-distribution of claudin-1 from the cytosol to the membrane and nucleus. Furthermore, TJ formation was stimulated, indicated by increased transepithelial electrical resistance. Silencing ZIP9 expression by siRNA prevented all of these responses. These results are consistent with an alternative pathway for testosterone action at the BTB that does not involve the nuclear AR and highlight the significant role of ZIP9 as a cell-surface androgen receptor that stimulates TJ formation.

2008 ◽  
Vol 20 (9) ◽  
pp. 31
Author(s):  
G. A. Tarulli ◽  
P. G. Stanton ◽  
K. Loveland ◽  
E. Rajpert De Meyts ◽  
R. I. McLachlan ◽  
...  

Recent studies suggest that adult Sertoli cells are not part of a homogenous and terminally differentiated population in phenotypes infertility1–4. The aims of this study were to compare the differentiation status of Sertoli cells from normal men undergoing gonadotrophin suppression by hormonal-based contraception (androgen plus progestin), as well as in pre-malignant and malignant testicular cancer. Confocal microscopy was performed to assess the expression of markers of cell proliferation (PCNA) and differentiation (androgen receptor) in Sertoli cells in all tissues. As additional markers of differentiation, Sertoli cell tight junction (claudin-11, JAM-A) and associated proteins (ZO-1) were assessed in men with testicular cancer. Samples from five different men were assessed in each group. In normal men, Sertoli cells exhibited a differentiated phenotype (i.e. PCNA negative, androgen receptor positive). However, after gonadotrophin suppression, 1.7 ± 0.6% of Sertoli cells exhibited intense PCNA reactivity and a reduction in androgen receptor immunoreactivity, demonstrating an undifferentiated phenotype. PCNA-positive Sertoli cells were never observed in pre-malignancy, and were only rarely observed in malignant testicular cancer, indicating a potential change in differentiation. Tight junction protein localisation was disrupted in pre-malignant cancer, with a reduction in JAM-A reactivity in Sertoli cells from pre-malignancy and strong JAM-A reactivity in malignant cancer; suggesting a potential role for JAM-A expression in the progression of testicular cancer. We conclude that Sertoli cells are not a homogenous and terminally differentiated population in men and their differentiation is modifiable by hormones and in the disease state. (1) Meachem et al. 2005, Biol Reprod. 72:1187–93 (2) Tarulli et al. 2006, Biol Reprod. 74:798–806 (3) Donner et al. 2004, APMIS. 112:79–88 (4) Brehm et al. 2006, Anat Embryol (Berl). 211(3):223–36


Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3922-3931 ◽  
Author(s):  
M. Carey Satterfield ◽  
Kathrin A. Dunlap ◽  
Kanako Hayashi ◽  
Robert C. Burghardt ◽  
Thomas E. Spencer ◽  
...  

In species with noninvasive implantation by conceptus trophectoderm, fetal/maternal communications occur across the endometrial epithelia. The present studies identified changes in junctional complexes in the ovine endometrium that regulate paracellular trafficking of water, ions, and other molecules, and the secretory capacity of the uterine epithelia. Distinct temporal and spatial alterations in occludin, tight junction protein 2, and claudin 1–4 proteins were observed in the endometrium of cyclic and early pregnant ewes. Dynamic changes in tight junction formation were characterized by an abundance of tight junction proteins on d 10 of the estrous cycle and pregnancy that substantially decreased by d 12. Early progesterone administration advanced conceptus development on d 9 and 12 that was associated with loss of tight-junction-associated proteins. Pregnancy increased tight-junction-associated proteins between d 14–16. Cadherin 1 and β-catenin, which form adherens junctions, were abundant in the endometrial glands, but decreased after d 10 of pregnancy in the luminal epithelium and then increased by d 16 with the onset of implantation. Results support the ideas that progesterone elicits transient decreases in tight and adherens junctions in the endometrial luminal epithelium between d 10–12 that increases selective serum and tissue fluid transudation to enhance blastocyst elongation, which is subsequently followed by an increase in tight and adherens junctions between d 14–16 that may be required for attachment and adherence of the trophectoderm for implantation. The continuous presence of tight and adherens junctions in the uterine glands would allow for vectorial secretion of trophic substances required for conceptus elongation and survival.


2018 ◽  
Vol 121 ◽  
pp. 42-52 ◽  
Author(s):  
Wei-Rong Yang ◽  
Ting-Ting Liao ◽  
Zi-Qiang Bao ◽  
Cai-Quan Zhou ◽  
Hong-Yan Luo ◽  
...  

2008 ◽  
Vol 295 (4) ◽  
pp. F867-F876 ◽  
Author(s):  
Susanne Angelow ◽  
Robert Ahlstrom ◽  
Alan S. L. Yu

Claudins are a family of tight junction membrane proteins that regulate paracellular permeability of epithelia, likely by forming the lining of the paracellular pore. Claudins are expressed throughout the renal tubule, and mutations in two claudin genes are now known to cause familial hypercalciuric hypomagnesemia with nephrocalcinosis. In this review, we discuss recent advances in our understanding of the physiological role of various claudins in normal kidney function, and in understanding the fundamental biology of claudins, including the molecular basis for selectivity of permeation, claudin interactions in tight junction formation, and regulation of claudins by protein kinases and other intracellular signals.


EBioMedicine ◽  
2014 ◽  
Vol 1 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Fatih M. Uckun ◽  
Hong Ma ◽  
Zahide Ozer ◽  
Patricia Goodman ◽  
Jian Zhang ◽  
...  

2017 ◽  
Vol 137 (4) ◽  
pp. 884-893 ◽  
Author(s):  
Elena Rahn ◽  
Katharina Thier ◽  
Philipp Petermann ◽  
Matthias Rübsam ◽  
Peter Staeheli ◽  
...  

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