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Tuesday, January 23, 2007

Screening Methods for Androgens Part 1a

Whole Animal Methods (In Vivo)
Intact animals used to measure androgenic activity (Allen and Doisy, 1924; Hershberger et al., 1953).
In vivo methods
- Take advantage of animal’s innate hormone-directed tissue development and maintenance responses and
- Use these responses to identify whether administered substances alter the normal response.
Animal’s inherent capacity to produce these hormones must be removed.
# Castration.
# Immature or juvenile animals used

(M. Chaturvedia, P.C. Mali, A.S. Ansarib; Pharmacology: 2003; 68:38-48)
For androgenicity evaluation of test subs. rats were divided into four groups:
Group I- animals were castrated 30 days before the experiment to serve as controls
Group II, III and IV subjected to castration 30 days before the experiments, followed by administration of test subs., testosterone propionate (0.01 mg/rat/alternate day s.c.), and test subs. with testosterone propionate, respectively, for 30 days.
Studied-- cauda epididymis sperm motility and density,
Number of pups,
Fertility,
The weights of testes, epididymis, seminal vesicle, and prostate
Histoarchitecture of the testes

Endocrine challenge test (ECT). (Anderson et al., 1992).
Bioassay - to evaluate gonadal response to a substance by measuring the steroid hormone production and release following administration of test subs.
The intact mature animal is challenged with GnRH or an LH- or FSH-like substance that stimulates a hormonal response.
Serial blood samples collected and measured to evaluate whether the substance being tested causes increased testosterone
Techniques used include tail vein sampling, tail vein treatments and/or jugular catheterization (Fail et al., 1995; Fail and Anderson, 2002).
A number of different endpoints have been used.
* Plasma testosterone, before (basal) and after stimulation. Testosterone concentrations measured by RIA (Fail et al., 1995; 1996).
*Epididymis weight, caudal sperm count, testicular sperm heads, and sperm motility
(Fail et al., 1995; 1996).

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