EFFECTS OF TETRAHYDROCANNABINOL ON SEXUAL DIMORPHISM OF RAT LIVER MIXED FUNCTION OXIDASE

Pregnant Sprague-Dawley rats were gavaged with vehicle (olive oil) or 37.5, 75, 150 or 300 mg/kg of (DELTA)('9)-Tetrahydrocannabinol (THC) on days 18 or 19 of gestation. Male offspring as well as a group of hypophysectomized rats (positive control) were sacrificed at 35 days of age, while females and hypophysectomized control were sacrificed at 36 days of age. The sex-differences in ethylmorphine-N-demethylase and aniline hydroxylase liver activities were evaluated.^ Ethylmorphine-N-demethylase activity showed a significant difference between males and females from control and 37.5, 75 and 150 mg/kg THC dosed groups. Female offspring exposed prenatally to 300 mg/kg THC had a significant increase (p < .01) in N-demethylation activity, while their male counterparts had similar enzyme activity to those found in the male groups from control and 37.5 to 150 mg/kg THC dosed. Moreover, the percent increase in the 300 mg/kg THC dosed females was similar to that detected in the hypophysectomized female rats (positive control). As expected no sex difference in aniline hydroxylase activity was detected in control as well as exposed groups, including the 300 mg/kg THC dosed group.^ It is concluded that (DELTA)('9)-Tetrahydrocannabinol administered once by gavage in days 18 or 19 of gestation alters the liver Mixed Function Oxidase (MFO) sexual dimorphism imprinting process of the rat. ^

GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B

DMRT (Doublesex and Mab-3 related transcription factor) proteins generally associated with sexual differentiation in many organisms share a common DNA binding domain and are often expressed in reproductive tissues. Aside from doublesex, which is a central factor in the regulation of sex determination, Drosophila possesses three different dmrt genes that are of unknown function. Because the association with sexual differentiation and reproduction is not universal and some DMRT proteins have been found to play other developmental roles we chose to further characterize one of these Drosophila genes. We carried out genetic analysis of dmrt93B, which was previously found to be expressed sex-specifically in the developing somatic gonad and to affect testis morphogenesis in RNAi knockdowns. In order to disrupt this gene, the GAL4 yeast transcriptional activator followed by a polyadenylation signal was inserted after the dmrt93B start codon and introduced into the genome by homologous recombination. Analysis of the knock-in mutation as well as a small deletion removing all dmrt93B sequence demonstrate that loss of function causes partial lethality at the late pupal stage. Surprisingly, these mutations have no significant effect on gonad formation or male fertility. Analysis of GAL4-driven GFP reporter expression indicates that the dmrt93B promoter activity is highly specific to neurons in the suboesophageal and proventricular ganglion in larva and adult of both sexes suggesting a possible role in digestive tract function. Using the Capillary Feeder (CAFÉ) assay to measure daily food intake we find that reduction in this gene’s function leads to an increase in food consumption. These results suggest dmrt93 plays an important role in the formation or maintenance of neurons that affect feeding and support the idea that dmrt genes may not be restricted to roles in sexual differentiation.

Behavioral and psychosocial factors associated with sexual risk in a population of crack cocaine users

The purpose of this dissertation was to examine the relationship between key psychosocial and behavioral components of the Transtheoretical Model and the Theory of Reasoned Action for sexual risk reduction in a population of crack cocaine smokers and sex workers, not in drug treatment. ^ The first study examined the results of an analysis of the association between two principal constructs in the Transtheoretical Model, the processes of change and the stages of change for condom use, in a high risk population. In the analysis of variance for all respondents, the overall F-test revealed that people in different stages have different levels of experiential process use, F(3,317) = 17.79, p = 0.0001 and different levels of behavioral process use, F(3,317) = 28.59, p = .0001. For the experiential processes, there was a significant difference between the precontemplation/contemplation stage, and both the action, and maintenance, stages.^ The second study explored the relationship between the Theory of Reasoned Action “beliefs” and the stages-of-change in the same population. In the analysis of variance for all participants, the results indicate that people in different stages did value the positive beliefs differently, F(3,502) = 15.38, p = .0001 but did not value the negative beliefs differently, F(3,502) = 2.08, p = .10. ^ The third study explored differences in stage-of-change by gender, partner type drug use, and HIV status. Three discriminant functions emerged, with a combined χ2(12) = 139.57, p = <.0001. The loading matrix of correlations between predictors and discriminant functions demonstrate that the strongest predictor for distinguishing between the precontemplation/contemplation stage and the preparation, action, and maintenance stages (first function) is partner type (.962). The loadings on the second discriminant function suggest that once partner type has been accounted for, ever having HIV/AIDS (.935) was the best predictor for distinguishing between the first three stages and the maintenance stage. ^ These studies demonstrate that behavioral change theories can contribute important insight to researchers and program planners attempting to alter HIV risk behavior in high-risk populations. ^

Sexually transmissible diseases, sexual factors and prostate cancer: A review of literature

A review of literature was carried out regarding sexually related factors, sexually transmissible diseases (STD's) and infections with prostate cancer (PC) development risk. The review of literature, in conjunction with the tabulation of studies, suggested that ejaculation and circumcision may play a protective role in the development of PC and that multiple sex partners and an active sex life may play a causal role in the development of PC which may negate and counteract the protective effects of ejaculation and circumcision. HIV infection may plausibly play a function in deteriorating and compromising immune controls on carcinogenesis. Because of the coexistence of a highly active sexual lifestyle and sexual promiscuity with the growing occurence of STD's, their maybe a correlation with the high incidence of prostate cancer in the United States. Potential multi-institutional studies are warranted to confirm the high incidence of this neoplasm with the increasing cases of STD's and if in fact there is a proportional association to further elucidate the factors responsible for its high incidence.^