It is the aim of this study to elucidate the influence of progesterone on body weight regulation in intact female rats. A study of the literature includes a description of the body weight regulation and the effects of ovarian hormones on it. The controlled-system approach tries to link behavioral and physiological factors altering energy balance. The experimental study is subdivided into food-intake - and food-selection studies, a locomotor activity study, a study eliciting a possible role of thermogenesis, and finally rat liver studies which consist of a gas chromatography analysis of hepatic fatty acids and an electron microscopy study examining the ultrastructure of hepatocytes. It can be concluded that the effect of progesterone treatment on the body weight of intact female rats depends on the route of administration. There is a significant increase in body weight after subcutaneous progesterone injections without changes in total caloric intake and nutrient selection habits, indicating the importance of energy expenditure. But changes in spontaneous activity make no contribution in the progesterone-induced energy storage. It is also concluded that peripherally located brown adipose tissue thermogenesis is not changed, without ruling out the effect of more centrally located thermogenic organs as the liver. In this organ, small but significant changes in the fatty acid profile occur during the subcutaneous progesterone treatment.

Two experiments were designed to hormonally induce spermatozoal abnormalities in the ejaculate specifically, those abnormalities associated with the cytoplasmic droplet syndrome. The endocrine response during and following hormone administration was monitored to determine if there was an association between the appearance of spermatozoal abnormalities and plasma hormone changes. During Experiment 1, one 7-yr-old and two yearling Holstein bulls were injected with 200 IU ACTH every 8 hr for 6 days. In Experiment 2, two groups of three yearling Holstein bulls each were injected daily with crystalline progesterone in propylene glycol (.84 mg/kg body wt) for 21 days. Semen characteristics (sperm abnormalities, percent motility, sperm concentration and ejaculate volume) were measured for each of four ejaculates collected weekly from each bull. Semen was collected 9 wk prior to hormone treatment, during and for 8 and 9 wk after the treatment period in Experiments 1 and 2, respectively. During Experiment 1, percent intact acrosomes were measured weekly. Tonometer measurements of testicular consistency were made weekly for each bull during Experiment 2. Blood samples were obtained prior to, during and after hormone treatment in both experiments. The hormonal response in total corticoids, testosterone and androstenedione was monitored in Experiment 1. During Experiment 2 corticoids, testosterone, LH and progesterone concentrations were monitored. Corticoid concentrations were determined by competitive protein binding; androstenedione, progesterone, LH and testosterone were determined by radioimmunoassay. In Experiment 1, mean (±SE) corticoid concentrations for all three bulls were elevated from 11.9±2.7 to 73.5±4.1 ng/ml during ACTH administration. Testosterone was suppressed in the yearling bulls from 5.5±.9 to 0.5±.5 ng/ml beginning 8 hr following the initial ACTH injection until 24 hr following the last injection. The mature bull maintained normal testosterone concentrations for the first four injection days, and then concentrations were suppressed for the last 2 days of injection. Although not significant, androstenedione concentrations for all bulls were elevated during treatment. Semen quality and sperm output were unaffected by ACTH treatment. In Experiment 2 progesterone administration increased plasma progesterone concentrations during and after treatment in both groups of bulls. There was a significant group by treatment interaction for progesterone. Endogenous (pre-treatment) progesterone levels were higher in Group 2 than in Group 1 (2.5±.4 vs 0.5±1.0 ng/ml). However, the magnitude of the progesterone response to treatment was higher in Group 1 than Group 2 (7.3±.9 vs 5.6±.3 ng/ml). In addition, testosterone and LH concentrations were significantly lowered during treatment. There was no change in corticoids. Although only two bulls in Group 1 and none of the bulls in Group 2 responded with increased abnormals, there was a significant increase in abnormals associated with progesterone treatment. Proximal, translocating and distal cytoplasmic droplets and detached sperm heads were the predominant abnormalities induced by progesterone treatment. Percent motility and ejaculate volume were significantly decreased for the three week period following progesterone treatment in both groups. Changes in sperm concentration and weekly sperm output were noted. No change in testicular tonicity was observed. There was no evidence of premature spermiation or change in frequency of the stages of the cycle of the seminiferous epithelium in testicular tissue from treated bulls. However, variation in acrosomal development and nuclear condensation was observed among syncytia of spermatids within the same cross section of a seminiferous tubule. This was not associated with progesterone treatment. / Ph. D.

This study examines the effect of progesterone-only injectable contraceptives, and medroxyprogesterone acetate (Depo-Provera) in particular, on the cells of the uterine cervix. Cervical and vaginal smears were taken before commencement of therapy and at 3 and 6 month intervals thereafter on 79 asymptomatic women attending a family planning clinic. Results of hormonal and cellular measurements before and after therapy were compared. menstrual cycling was also studied. The effect on Methods used were hormonal maturation indices, image analysis measurements and microscopic observation of cellular . features. The latter included anisocytosis, anisokaryosis, karyomegaly , plaque formation, cytoplasmic wrinkling, nuclear grooving, hypertrophy, atrophy, cytoplasmic moulding and density, retarded maturation and nuclear protrusions. Squamous, endocervical and metaplastic cells were examined. Analysis of the results showed that progesterone-only contraceptives produce all of the above to a greater or lesser degree resulting in an increased relative nuclear area which may be confused with intraepithelial neoplasia. This is due to the production of a folate deficiency at target organ level which interferes with cell division and slows the maturation process. This effect enabled further observations to be made leading to the establishment of the origin and content of the nipple-like protrusions which occur in endocervical cells in response to hormonal activity. Physiological effects included amenorrhoea and irregular menstrual cycling. Most women showed evidence of interference with normal cycling to a varying degree. The documented cellular changes were shown to modify the expression of common inflammatory and neoplastic conditions of the uterine cervix. These included trichomoniasis, herpesvirus cervicitis, human papillomavirus infection, folate deficiency, cervical intraepithelial neoplasia and invasive carcinoma as well as multiple pathologies. The potential for diagnostic error was examined. New diagnostic criteria were formulated based on the comparison of cellular features found in the presence of the contraceptive with those found under normal conditions. It is anticipated that these criteria will facilitate the cytological diagnosis of pathological conditions of the uterine cervix in users of depo-medroxyprogesterone acetate (DMPA), leading to increased accuracy and improved and better directed patient management. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1993.