Effects of androstenedione on in utero development in rats

Abstract

This study was conducted to characterize the effect of androstenedione on estrous cyclicity, mating behavior and fetal development. Thirty-day old rats received corn oil alone or androstenedione (in corn oil) at one of four concentrations (0, 1.0, 5.0, 10.0 or 30.0 mg/kg body weight) by gavage for two weeks prior to mating, during the mating period and throughout gestation. Dose related increases in serum androstenedione, estradiol and estrone were observed in all androstenedione treated animals at gestation day 20. A statistically significant increase in serum testosterone concentration was observed in the 30 mg/kg dose group. Feed and fluid consumption were not affected by androstenedione treatment during the pre-mating or gestational periods, however a statistically significant decrease in the number of females with regular estrous cycles was observed in the 10.0 and 30.0 mg/kg dose groups. Exposure to androstenedione did not affect mean body weight gain during pre-mating or gestation. Slight not statistically significant reductions in the number of implants, number of viable fetuses and number of viable male fetuses were observed in the 30.0 mg/kg androstenedione group. Reductions were not observed in the number of corpora lutea. Fetal growth in terms of fetal weight, crown-rump length, anogenital distance and the number of external abnormalities was not affected by androstenedione exposure. At the doses given, androstenedione had no specific effect on the development of individual bones, including sternebrae. Dose related effects of androstenedione were not observed on the development of soft tissues. A statistically significant increase in moderately enlarged ureter at the kidney was observed in both the 1.0 and 5.0 mg/kg dose groups. Organ weights (expressed per gram of body weight or per gram of brain weight) were not affected by androstenedione treatment.

Introduction

Anabolic steroids are commonly utilized to treat people who have a hormone deficiency or who have muscle wasting due to cancer or HIV. They have also been utilized as performance enhancing drugs to increase muscle strength and size for competitive sports. Most anabolic steroids are available only by prescription and their availability is tightly controlled (Anabolic Steroid Control Act, 1990). However, the use of steroid supplements to enhance athletic performance has become popular. Steroid supplements are utilized not only because many believe that these supplements can be converted into testosterone or a similar compound in the body, but because, as dietary supplements, they are easily accessible and can be purchased through various commercial sources. One steroid supplement, androstenedione, has become popular because several well known athletes have admitted using it to enhance their athletic performance. Androstenedione is a naturally occurring steroid hormone produced either by the adrenal glands or gonads and can be converted to either testosterone by the enzyme 17 beta-hydroxysteroid dehydrogenase or to an estrogen (i.e., estradiol or estrone) by the aromatase enzyme. It is sold in health food stores in the form of percutaneous gels, transdermal patches and chewing gums.

The use of steroid/steroid precursors/steroid supplements to elevate testosterone and possible estrogen levels may lead to adverse consequences such as liver and kidney damage in both males and females; acne, premature baldness, gynecomastia, enlarged prostate and reduced sperm production in males; and a disrupted menstrual cycle, deepened voice, increased facial hair growth (hirsutism) and clitomegaly in females (McEvoy, 1995). Use by children can lead to early puberty and premature cessation of bone growth.

Steroid use by high school and college students has been documented (Buckley et al., 1988, Terney and McLain, 1990, NIDA, 2000), and it has recently been reported that the use of steroids now extends to children and young adolescents even though this population is aware of the potential adverse effects of steroid use (Faigenbaum et al., 1998). Studies of self-reported use show that a significant number of adolescents have experimented with anabolic-androgenic steroid use (Yesalis et al., 1993, Yesalis, 1997) and it has been reported that steroid abuse by junior high and high school girls doubled between 1991 and 1998 (Yesalis, 1998). It has been suggested that this increase in steroid abuse may reflect increased athletic opportunities for young women and an increased interest in self-image among teen-age girls. It has also been suggested that a lean muscular “hard body” image popular among actresses and models may be prompting young girls to imitate these so-called ideal body images. Many teen age girls now desire to look healthier and somewhat more muscular, and this has led some girls toward an unhealthy compulsion to be ever fitter with larger muscles (Yesalis, 1998). Unfortunately, there is very little prospective data available regarding the safety of most steroid supplements. The following study was conducted in order to characterize the effects of androstenedione, a model steroid supplement, on female reproductive function using rats as an experimental model. The objectives of this study were: (1) to characterize the effect of androstenedione exposure on estrous cyclicity and mating behavior in young animals, and (2) to characterize the effect of gestational exposure to androstenedione on fetal development.