170. THE ROLE OF MEGALIN IN PROSTATE DEVELOPMENT OF THE MOUSE

2010 ◽  
Vol 22 (9) ◽  
pp. 88 ◽  
Author(s):  
M. Gamat ◽  
G. Shaw ◽  
M. B. Renfree
Keyword(s):  
Cell Membrane ◽  
Knockout Mice ◽  
Sex Steroids ◽  
Urogenital Sinus ◽  
Sex Steroid ◽  
Testicular Descent ◽  
Mouse Prostate ◽  
Bud Induction ◽  
Bud Initiation

Prostatic development is dependent on androgens; but the precise mechanism by which androgens mediate their effect is still unclear. Megalin, a cell membrane transporter, may shuttle sex steroids into cells to regulate androgen-responsive genes responsible for prostatic bud induction in the urogenital sinus (UGS). In megalin knockout mice, testicular descent fails and the vagina fails to open in females, both of which are dependent on sex steroid signalling (Hammes et al. 2005) . In this megalin-mediated pathway, SHBG-bound sex steroids bind to megalin, which is internalised. The SHBG-sex steroid complex is released, and the sex steroid is released from SHBG where it can bind to the androgen receptor to regulate androgen responsive genes. Receptor-Associated Protein (RAP) is a molecular chaperone protein that protects newly synthesised megalin from binding to potential ligands in the cytoplasm prior to insertion into the cell membrane. We hypothesised that megalin may shuttle SHBG-bound androgens across the cell membrane. This study characterised the expression and evaluated a possible role for megalin in the development of the mouse prostate. Megalin, SHBG and RAP transcripts were detected in the developing male and female UGS of the mouse from day E14.5 to day E18.5 (when prostatic buds start to form) and in the adult prostate. Megalin, SHBG and RAP protein were localised in the urogenital epithelium. To assess the role of megalin in prostatic development, UGS tissues were incubated with androgens in the presence and absence of RAP. Incubating UGS tissues with RAP did NOT inhibit prostatic bud initiation. Furthermore, in the UGS of megalin knockout mice, prostatic bud formation appeared to be identical to those of wild-type littermates. These results demonstrate that megalin is not involved in prostatic bud initiation. However, the ubiquitous expression of megalin suggests that its role is redundant in the prostate. (1) Hammes A et al. (2005) Role of endocytosis in cellular uptake of sex steroids. Cell 122(5), 751–62.

Role of GM-CSF in a mouse model of experimental autoimmune prostatitis

2019 ◽  
Vol 317 (1) ◽  
pp. F23-F29 ◽  
Author(s):  
Yaxiao Liu ◽  
Yan Li ◽  
Qinggang Liu ◽  
Zonglong Wu ◽  
Jianfeng Cui ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dorsal Root Ganglia ◽  
Knockout Mice ◽  
Dorsal Root ◽  
Prostate Tissue ◽  
Mrna Levels ◽  
Gm Csf ◽  
Mouse Prostate ◽  
Experimental Autoimmune

The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in patients with CP/CPPS and in a mouse model of experimental autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from patients with CP/CPPS and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal root ganglia were determined using PCR and immunohistochemistry. Behavioral testing and inflammation scoring were performed to evaluate the role of GM-CSF in disease development and symptom severity of EAP using GM-CSF knockout mice. mRNA levels of putative nociceptive and inflammatory markers were measured in the prostate after the induction of EAP. Elevated GM-CSF mRNA levels were observed in expressed prostatic secretions samples from patients with CP/CPPS compared with healthy volunteers. GM-CSF mRNA was also significantly increased in prostate tissue of the EAP mice model. The expression of GM-CSF receptors was confirmed in mouse prostate and dorsal root ganglia. GM-CSF knockout mice showed fewer Infiltrating leukocytes and pain symptoms after the induction of EAP. Deletion of GM-CSF significantly diminished EAP-induced increases of chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3, and nerve growth factor mRNA expression. The results indicated that GM-CSF plays a functional role in the pathogenesis of EAP. GM-CSF may function as a signaling mediator for both inflammation and pain transduction in CP/CPPS.

Sex steroids-induced neurogenesis in adult brain: a better look at mechanisms and mediators

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamideh Abotalebi ◽  
Babak Ebrahimi ◽  
Raziyeh Shahriyari ◽  
Reyhaneh Shafieian
Keyword(s):  
Sex Steroids ◽  
Ventricular Zone ◽  
Mammalian Species ◽  
Adult Brain ◽  
Sex Steroid ◽  
Subgranular Zone ◽  
Human Beings ◽  
The Relationship ◽  
The Brain

Abstract Adult neurogenesis is the production of new nerve cells in the adult brain. Neurogenesis is a clear example of the neuroplasticity phenomenon which can be observed in most of mammalian species, including human beings. This phenomenon occurs, at least, in two regions of the brain: the subgranular zone of the dentate gyrus in hippocampus and the ventricular zone of lateral ventricles. Numerous studies have investigated the relationship between sex steroid hormones and neurogenesis of adult brain; of which, mostly concentrated on the role of estradiol. It has been shown that estrogen plays a significant role in this process through both classic and non-classic mechanisms, including a variety of different growth factors. Therefore, the objective of this review is to investigate the role of female sex steroids with an emphasis on estradiol and also its potential implications for regulating the neurogenesis in the adult brain.

scholarly journals Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

2000 ◽  
Vol 25 (1) ◽  
pp. 1-16 ◽  
Author(s):  
F Labrie ◽  
V Luu-The ◽  
SX Lin ◽  
J Simard ◽  
C Labrie ◽  
...  
Keyword(s):  
Human Physiology ◽  
Postmenopausal Women ◽  
Sex Steroids ◽  
Sex Steroid ◽  
Peripheral Target ◽  
Adult Men ◽  
Hydroxysteroid Dehydrogenases ◽  
The Family ◽  
Site Of Action

In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs) while different 17 beta-HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 beta-HSDs have been cloned, sequenced and characterized. The 17 beta-HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.

scholarly journals Sexually dimorphic effects of morphine and MK-801: sex steroid-dependent and -independent mechanisms

2002 ◽  
Vol 92 (2) ◽  
pp. 493-503 ◽  
Author(s):  
Deborah N. D'Souza ◽  
Richard E. Harlan ◽  
Meredith M. Garcia
Keyword(s):  
Gender Differences ◽  
Sex Steroids ◽  
Behavioral Responses ◽  
Gonadal Steroids ◽  
Sex Steroid ◽  
Sexually Dimorphic ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Steroid Dependent

Rats show gender differences in responses to morphine and the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.

Role of ovarian sex steroids in the regulation of thyrotropin (TSH) secretion of hypogonadal women

1992 ◽  
Vol 127 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Winfried G Rossmanith ◽  
Claudia Stäbler ◽  
Reiner Benz ◽  
Stefan R Bornstein ◽  
Werner A Scherbaum
Keyword(s):  
Postmenopausal Women ◽  
Sex Steroids ◽  
Interindividual Variability ◽  
Sex Steroid ◽  
Neuroendocrine Regulation ◽  
Exact Role ◽  
Study Condition ◽  
Tsh Secretion ◽  
Total Triiodothyronine

The exact role of ovarian sex steroids in the neuroendocrine regulation of thyrotropin (TSH) release in women can only be accurately assessed in the absence of any considerable ovarian sex steroid feedback upon the hypothalamic-pituitary unit. Consequently, the unstimulated episodic and thyrotropin-releasing hormone (TRH) stimulated TSH secretion was evaluated in postmenopausal women before and during sequential ovarian sex steroid replacements. Seven euthyroid women (mean age: 59.4 years) were studied initially without any sex steroid replacement (control studies), then on the last day of a 21-day course of oral estradiol-valeriate (E2) administration (2 mg daily) and finally, on the last day of a 21-day course of oral estradiol-progesterone (E2/P4) replacement (2 mg E2 and 200mg micronized P4 daily). During all study occasions, blood was sampled at 10 min intervals for 10 h, while TRH (200 μg iv) was administered 8 h after initiation of blood collections. Compared to the control conditions, serum E2 and P4 concentrations markedly increased (p< 0.001) following oral E2 or E2/P4 treatments. Total triiodothyronine (T3) and thyroxine (T4) concentrations and free T3 and T4 equivalents remained unchanged during E2 and E2/P4 regimens. In the unstimulated secretory profiles, TSH was found to be episodically released, with little interindividual variability for each study condition. Since the TSH pulse attributes (pulse amplitudes, frequencies, interpulse intervals, mean TSH concentrations, by Cluster pulse algorithm) did not significantly change during E2 and E2/P4 replacements, the episodic character of TSH secretion virtually remained unchanged by sex steroid replacements. In addition, the TRH-stimulated TSH releases during E2 and E2/P4 replacement therapies closely resembled those during control conditions. These observations demonstrate that both the unstimulated episodic and TRH-stimulated TSH secretion are unaffected by ovarian sex steroid replacement in hypogonadal women. Collectively, our findings suggest that ovarian sex steroids may not be critically involved in the neuroendocrine regulation of TSH secretion in women.

The role of (bio)surfactant sorption in promoting the bioavailability of nutrients localized at the solid-water interface

1999 ◽  
Vol 39 (7) ◽  
pp. 91-98 ◽  
Author(s):  
Ryan N. Jordan ◽  
Eric P. Nichols ◽  
Alfred B. Cunningham
Keyword(s):  
Mass Transfer ◽  
Cell Membrane ◽  
Substrate Concentration ◽  
Water Interface ◽  
Industrial Systems ◽  
Solid Liquid Interface ◽  
Solid Liquid ◽  
Surfactant Sorption

Bioavailability is herein defined as the accessibility of a substrate by a microorganism. Further, bioavailability is governed by (1) the substrate concentration that the cell membrane “sees,” (i.e., the “directly bioavailable” pool) as well as (2) the rate of mass transfer from potentially bioavailable (e.g., nonaqueous) phases to the directly bioavailable (e.g., aqueous) phase. Mechanisms by which sorbed (bio)surfactants influence these two processes are discussed. We propose the hypothesis that the sorption of (bio)surfactants at the solid-liquid interface is partially responsible for the increased bioavailability of surface-bound nutrients, and offer this as a basis for suggesting the development of engineered in-situ bioremediation technologies that take advantage of low (bio)surfactant concentrations. In addition, other industrial systems where bioavailability phenomena should be considered are addressed.

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