THE ROLE OF TESTOSTERONE AND ANDROSTENEDIONE AS PRECURSORS OF EPITESTOSTERONE IN GUINEA PIGS (IN VIVO AND IN VITRO STUDIES)

1971 ◽  
Vol 67 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Marian Szamatowicz ◽  
Michel Drosdowsky ◽  
Max F. Jayle

ABSTRACT After injection of [7α-3H] androstenedione and [4-14C] testosterone into male and female guinea pigs, doubly labelled aetiocholanolone, 5α-androstanedione and epiandrosterone were identified in the urine. No epitestosterone was detected. Ovaries, testes, adrenals and liver slices were incubated with the same precursors. Epitestosterone production was observed in all organs except in the adrenals. According to the epitestosterone 3H/14C ratio, it can be concluded that in guinea pigs an interconversion of testosterone, androstenedione and epitestosterone takes place. In liver, androstenedione is preferentially converted to epitestosterone without sex differences, whereas in ovary and testis epitestosterone derives preferentially from testosterone.

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.


Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2513-2517 ◽  
Author(s):  
K Hamamura ◽  
H Matsuda ◽  
Y Takeuchi ◽  
S Habu ◽  
H Yagita ◽  
...  

Hematopoiesis requires specific interactions with the microenvironments, and VLA-4 has been implicated in these interactions based on in vitro studies. To study the role of VLA-4 in hematopoiesis in vivo, we performed in utero treatment of mice with an anti-VLA-4 monoclonal antibody. Although all hematopoietic cells in fetal liver expressed VLA-4, the treatment specifically induced anemia. It had no effect on the development of nonerythroid lineage cells, including lymphoids and myeloids. In the treated liver almost no erythroblast was detected, whereas the erythroid progenitors, which give rise to erythroid colonies in vitro, were present. These results indicate that VLA-4 plays a critical role in erythropoiesis, while it is not critical in lymphopoiesis in vivo.


2009 ◽  
Vol 186 (3) ◽  
pp. 355-362 ◽  
Author(s):  
Delphine Mérino ◽  
Maybelline Giam ◽  
Peter D. Hughes ◽  
Owen M. Siggs ◽  
Klaus Heger ◽  
...  

Proteins of the Bcl-2 family are critical regulators of apoptosis, but how its BH3-only members activate the essential effectors Bax and Bak remains controversial. The indirect activation model suggests that they simply must neutralize all of the prosurvival Bcl-2 family members, whereas the direct activation model proposes that Bim and Bid must activate Bax and Bak directly. As numerous in vitro studies have not resolved this issue, we have investigated Bim's activity in vivo by a genetic approach. Because the BH3 domain determines binding specificity for Bcl-2 relatives, we generated mice having the Bim BH3 domain replaced by that of Bad, Noxa, or Puma. The mutants bound the expected subsets of prosurvival relatives but lost interaction with Bax. Analysis of the mice showed that Bim's proapoptotic activity is not solely caused by its ability to engage its prosurvival relatives or solely to its binding to Bax. Thus, initiation of apoptosis in vivo appears to require features of both models.


1971 ◽  
Vol 134 (1) ◽  
pp. 176-187 ◽  
Author(s):  
Michael M. Frank ◽  
Joseph May ◽  
Thelma Gaither ◽  
Leonard Ellman

In vitro studies were performed utilizing sera from a strain of guinea pigs with a total absence of hemolytically active C4. Previous studies in these animals have demonstrated normal complement-dependent inflammatory reactions, suggesting that they are able to bypass their deficiency of C4. In vitro studies with C4-deficient serum also indicate normal activation of late-acting C components. Thus, endotoxin was capable of fixing normal amounts of the late components of complement (C3-9) in these sera, but did not fix C1 and C2. Antigen-antibody complexes fixed both early and late components of complement, although components beyond C4 were fixed less efficiently than in normal sera. Therefore, both in vivo and in vitro evidence indicates that the C4-deficient guinea pigs possess an alternate pathway for activation of late-acting complement components. Antigenic analysis of C4-deficient serum utilizing both guinea pig anti-C4 antibody and rabbit anti-C4 antibody suggests an absolute deficiency of C4-like molecules. Sera from animals with C4-deficiency were found to have one-half the normal level of C2. Sera from five of eight animals tested had 10–20% normal C1 activity. C3-9 assayed as a complex was normal.


2000 ◽  
Vol 118 (4) ◽  
pp. A732-A733
Author(s):  
Gerardo Nardone ◽  
Eileen Holicky ◽  
Jim R. Uhl ◽  
Vittorio Colantuoni ◽  
Lina Sabatino ◽  
...  

Author(s):  
Ismail Hadisoebroto Dilogo ◽  
Jessica Fiolin

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome. Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018 Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis. Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review. Results: Three tables of studies were constructed for in vitro studies and in-vivo studies. Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.


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