Physiological responses associated with sustained delivery of T, DHT, and AED in male rats.
The factors responsible for the marked gender difference in the risk of coronary heart disease and remain controversial. Several clinicians and basic scientists support the hypothesis that a protective effect of endogenous estrogen is the key, however epidemiological data failed to prove this trend. The role of endogenous androgens or sex steroid hormones on the development of atherosclerosis has received little attention over the years. The specific objectives of this study are: 1) to deliver testosterone (T), dihydrotestosterone (DHT), or androstenedione (AED) at sustained levels by tricalcium phosphate lysine (TCPL) ceramic delivery devices, and 2) to quantify major biochemical markers levels such as lactate dehydrogenase activity (LDH), total cholesterol, thiobarbituric reactive species associated with sustained delivery of androgens and 3) to evaluate the histopathological changes in vital and reproductive organs associated with excess androgens delivery in adult intact male rats. A total of sixteen male rats were randomly divided into four equal groups. Rats in group I served as intact controls, and animals in groups II-IV were implanted with a single TCPL delivery device contained T (40 mg), DHT (40 mg), or AED (40 mg), respectively. Animals in all groups were weighed and blood was drawn biweekly for cholesterol, LDH and TBAR analysis. At the end of ninety days post implantation, the animals were sacrificed and the organs removed, processed embedded, sectioned and screened for morphological changes. The results of this study suggest that: 1) sustained deliver of androgens caused a statistically significant increase (p < 0.05) in the prostate and the seminal vesicle weights, while the epididymis weights remained similar to control intact animals, 2) decreases in adrenal gland weight was detected in animals treated with androgens compared to control animals, 3) kidney weights increased in all androgen groups compared to control, 4) no differences were observed in heart, spleen, or body weights between the groups, 5) TBAR analysis, as well as LDH activity were not different between androgen treated animals and control animals, and 6) total cholesterol was significantly reduced in T and DHT treated groups compared with control and AED treated animals. The decrease in total cholesterol and reduction in adrenal gland weight may suggest impairment of cholesterol synthesis. In conclusion, this study provides information on the effects of sustained release of DHT, T and AED on the reproductive organs, vital organs, as well as physiological parameters such as TBARS (cellular damage) and total cholesterol.
Stokes
K I
KI
Jackson State University, MS 39204, USA.
Benguzzi
H A
HA
Cameron
J A
JA
D000735:Androstenedione / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D002130:Calcium Phosphates; D002516:Ceramics; D013196:Dihydrotestosterone / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004343:Drug Implants; D005837:Genitalia, Male / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008239:Lysine; D008297:Male; D010710:Phosphates; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage* / Q000494:pharmacology
D002130:Calcium Phosphates; D004343:Drug Implants; D008074:Lipoproteins; D010710:Phosphates; C112656:tricalcium phosphate lysine; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D007770:L-Lactate Dehydrogenase; D008239:Lysine