EFFECTS OF SHORT-TERM BILATERAL AND UNILATERAL CASTRATION AND ANDROGEN REPLACEMENT ON THE METABOLISM OF [3H]TESTOSTERONE IN VITRO BY THE EPIDIDYMIS OF THE IMMATURE RAT

1981 ◽  
Vol 91 (1) ◽  
pp. 53-60 ◽  
Author(s):  
R. G. FOLDESY ◽  
J. H. LEATHEM

The in-vitro metabolism of [3H]testosterone by the epididymis of the pubertal rat (55 days of age) has been examined after short-term bilateral and unilateral castration and androgen replacement. Bilateral castration did not decrease the metabolism of [3H]testosterone, but did result in a decline in the proportion of 5α-dihydrotestosterone produced and an increase in that of 5α-androstane-3α,17β-diol, androsterone and 5α-androstane-3,17-dione. Changes in metabolism occurred in the caput within 2 days after surgery, but not until 5 days after surgery in the cauda epididymidis. Daily testosterone treatment, which maintained prostatic growth in bilaterally castrated animals, did not restore normal androgen metabolism and increased further the production of androsterone and 5α-androstanedione by the cauda. In unilaterally castrated animals, androgen metabolism in epididymal tissue from the operated side was normal in the cauda but was indistinguishable in the caput from that of bilaterally castrated rats. These results indicate that (a) androgen metabolism by the caput, compared to that by the cauda, responds more quickly to androgen withdrawal and (b) that in the short term, normal androgen metabolism by the caput, but not the cauda, is dependent upon the presence of the ipsilateral testis. Furthermore, testosterone alone proved an inadequate replacement for bilateral castration which implies that the pubertal rat testis secretes additional compounds which are essential for normal function of the epididymis.

1988 ◽  
Vol 254 (4) ◽  
pp. G610-G621
Author(s):  
D. J. Ahnen ◽  
T. A. Reed ◽  
J. M. Bozdech

A nonenzymatic method is described for the isolation of viable populations of mature and immature rat colonocytes. Histology was used to monitor colocyte dissociation and to systematically characterize the amount of cross-contamination between populations of mature luminal cells and immature crypt cells. The mature colonocytes were 87 +/- 9% pure with respect to contamination from cells from the lower half of the colonic crypt, and the immature populations were 98% pure with respect to contamination with cells from the upper half of the colonic crypt. Neither population contained significant numbers of cells from the lamina propria. Cell viability and synthetic function were maintained for 10-12 h in short-term culture. Alkaline phosphatase activity was 1.59 +/- 0.01-fold higher in the mature cells than in the immature cells, and in vivo [3H]thymidine incorporation was 2.9 +/- 0.4-fold greater in the immature than the mature populations. Immature colonocytes synthesized protein in vitro at a rate of 2.5 +/- 0.4-fold higher than the mature cells, whereas fucoprotein synthetic rates and the secretory products were comparable in the two populations. Cell surface iodination revealed that the major iodinatable cell surface proteins were common to both cell populations. These studies demonstrate that highly enriched populations of mature and immature rat colonocytes that maintain viability and synthetic function in short-term culture can be prepared. The intrinsic rate of protein synthesis is higher in immature colonocytes, and a shift to synthesis of a higher percentage of fucoproteins occurs during colonocyte differentiation. In contrast to results in the small intestine, only modest gradients of differentiation markers and cell surface protein expression were observed between mature and immature colonocytes.


1981 ◽  
Vol 91 (1) ◽  
pp. 43-51 ◽  
Author(s):  
R. G. FOLDESY ◽  
J. H. LEATHEM

We examined the production in vitro of 5α-reduced metabolites from testosterone by the rat epididymis during pubertal maturation. Minced caput and cauda epididymides from 30-, 45-, and 55-day-old rats were incubated with [3H]testosterone for 2 h. Analysis of the radioactive metabolites revealed both similarities and differences in the metabolic patterns compared to those reported for adult rats. As in adults, 5α-dihydrotestosterone was the most abundant metabolite produced by both epididymal segments at all three ages, and it was formed in larger quantities in the caput epididymidis than in the cauda. However, [3H]testosterone metabolism by the epididymis of the immature rat was characterized by a lower formation of 5α-androstane-3α,17β-diol and higher production of 5α-androstane-3,17-dione than in adults. Production of these two metabolites by the caput region increased and decreased respectively, toward adult levels, with increasing age. In addition, the amount of [3H]testosterone metabolized was higher with tissues from prepubertal rats (30 days of age) than with those from rats 55 days of age. These data suggest that testosterone metabolism in the caput begins to change to that of the adult during the period of pubertal maturation but apparently not until later in the cauda epididymidis.


1993 ◽  
Vol 57 (2) ◽  
pp. 189-194 ◽  
Author(s):  
María B. Campos ◽  
Sara R. Chiocchio ◽  
Ricardo S. Calandra ◽  
Mónica N. Ritta

1984 ◽  
Vol 50 (2) ◽  
pp. 191-194
Author(s):  
J. L. Gelly ◽  
J. L. Delongeas ◽  
E. Barrat ◽  
R. Hatier ◽  
G. Grignon

Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


2001 ◽  
Vol 28 (4M) ◽  
pp. 32-39 ◽  
Author(s):  
Mary-Ellen Taplin ◽  
Glenn J. Bubley ◽  
Barur Rajeshkumar ◽  
Todd Shuster ◽  
Yoo-Joung Ko ◽  
...  

1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.


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