Estrogen interconversions in the induced cycle in female rhesus monkeys

To determine the extractions and interconversions of estrone and estradiol across and within the uterus, [3H]estradiol and [14C]estrone were infused at a constant rate in six ovariectomized female rhesus (Macaca mulatta) monkeys. Studies were done on Days 9, 14, and 23 of artificial menstrual cycles induced by the timed insertion and removal of Silastic capsules of estradiol and progesterone. Measurements of estrogen radioactivity were made from peripheral arterial blood and uterine venous blood as well as from endometrial biopsy samples. A significant increase occurred in the conversion of estradiol to estrone measured within the uterus on Day 23 compared to Days 9 and 14. The conversion of estrone to estradiol, measured within the uterus, fell progressively from Day 9 to Day 23, but this decrease was not significant. The extractions and interconversions across the uterus, and the overall interconversions of estrone and estradiol were not significantly different on Days 9, 14, or 23 of the cycle. Thus, we have been able to confirm in vivo the increase in the activity of the 17 beta-hydroxysteroid dehydrogenase, the enzyme responsible for estradiol to estrone interconversions, shown earlier by studies done in vitro. However, the increase in 17 beta-hydroxysteroid activity in the uterus is not reflected in the overall interconversions of estrone and estradiol as reflected by measurements in peripheral arterial blood.     

Effect of cyproterone acetate on prolactin secretion in the female rhesus monkey

Summary Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.Supported in part by USPHS Grant AM12583     

The effects of ovariectomy and progesterone on peripheral aromatization in the female rhesus monkey

We investigated the acute effects of surgery, i.e. ovariectomy, the long-term effects of ovariectomy, and the effects of progesterone on the peripheral aromatization of androstenedione in rhesus monkeys (Macaca mulatta). For the acute effects of surgery, 7 rhesus monkeys were given a pulse of [³H]androstenedione/[¹⁴C]estrone 2 weeks before and immedately after ovariectomy. In each case all urine was collected for 4 days and analyzed for radioactivity as estrone glucuronide and the peripheral aromatization calculated from the isotope ratios. Similarly, 5 monkeys were studied before and 18 months after ovariectomy. The acute effects of surgery resulted in a significant decrease in the peripheral aromatization of androstenedione to estrone from a mean±SE of 0.94 ± 0.26 to 0.61 ± 0.19%, P = 0.0452. Conversely, the long-term effects of ovariectomy resulted in a significant increase in peripheral aromatization from 0.38 ± 0.06 to 0.67 ± 0.12%, P = 0.0207. In 7 monkeys the peripheral aromatization was measured before and 10 days after the administration of progesterone, 100 mg in oil. There was no difference in peripheral aromatization before, 0.62 ± 0.04% and after progesterone, 0.58 ± 0.05%, P = 0.10. We conclude that the acute stress of ovariectomy, or possibly the loss of ovarian aromatizing tissue, results in a decline in peripheral aromatization, but ovariectomy will have the long-term effect of an increase in aromatization, and that the presence or absence of progesterone does not play a role.     

Cryptococcal dermotropism in the rhesus monkey

An unexpected result was obtained from the intravenous injection ofCryptococcus neoformans into rhesus monkeys. We had sought to develop pulmonary lesions, but instead cutaneous lesions occurred.Each of seven monkeys received five millionCryptococcus neoformans cells intravenously. On the ninth to fifteenth day an acneform cutaneous eruption and nodular sub-cutaneous swellings appeared in all the monkeys and disappeared spontaneously by about the thirtieth day. Biopsies on the ninth day showed free cryptococcal cells with polymorphonuclear response. Biopsy on the twenty-second day showed persistent abscesses with a surrounding shell of giant cells containing shrunken and partially digested cryptococcal organisms. Chest x-rays on the fifteenth day showed no pulmonary lesions. None of the monkeys died spontaneously. When they were sacrificed between the 37th and 102nd day, the lungs were devoid, both grossly and microscopically, or cryptococcal lesions. However, a fulminating cryptococcosis of the right bulbus oculi was found on one monkey and a minute cryptococcal granuloma in the brain of another. Skin testing with cryptococcin was negative before the experimental injection, but became positive at three weeks. Reinjection ofC. neoformans i.v. in one of the monkeys resulted in a second crop of dermal lesions, though of smaller extent and of shorter duration.The 39.5° C temperature of the rhesus monkey may be a factor in the paucity of pulmonary lesions and the development of cutaneous ones.Aided by Grant AI 08454, Department of Health, Education and Welfare, U.S. Public Health Service. Presented at the Annual Meeting of the American Society for Microbiology, Minneapolis, Minn., May 2–7, 1971.     

Inter-group consorting by a free-ranging female rhesus monkey (Macaca mulatta)

The behavior of a free-ranging female rhesus monkey (XJ) who emigrated from her natal group (J) to another (M) for 14 consecutive days is described. Hypotheses as to its function and motivation are considered.     

Androgen metabolism in the rhesus monkey.

A mixture of 3H-testosteron (T) and 14C-4-androstene-3, 17-dione (A) was injected intravenously into 2 (I and II) rhesus monkeys (Macaca mulatta). A third monkey (III) was injected with 3H-T only. Urine and bile samples were collected at intervals for 6 hours following the injection. The excretion, conjugation and aglycone metabolites of the steroids injected were studied using these samples. Of the injected dose, animal I (male) excreted 32% 3H and 23% 14C in the bile and 30% 3H and 21% 14C in the urine in 6 hours. Animal II (female), however, had a comparatively higher biliary excretion (66% 3H, 40% 14 C), but a urinary excretion (18% 3H, 13% 14C) comparable to that of animals I and III. The averages in the bile of the 3 animals were: unconjugated compounds 3%, glucosiduronates 78%, sulfates 9%, sulfoglucosiduronates 5% and disulfates 3%; and in urine, 5% unconjugated, 92% glucosiduronates and 3% sulfates. The aglycones obtained following hydrolysis were separated gy chromatography on Lipidex 5000, further purified by thin layer and paper chromatography and identified by co-crystallization. The major matabolites from 3H-T were androsterone and 5beta-androstane-3alpha,17beta-diol, whereas that from 14C-A was androsterone. Other metabolites identified were: etiocholanolone (3beta-hydroxy-5-beta-androstan-17-one); T, epitestosterone (epi-T), (17alpha-hydroxy-4-androsten-3-one); epiandrosterone (3-beta-hydroxy-5alpha-androstan-17-one) and 5alpha-androstane-3alpha, 17beta-diol. The results indicate that while androgen metabolism in the rhesus monkey is similar to that of the baboon and human in conjugate and metabolite formation, the rate of excretion was significantly different, resembline more closely that of the baboon than the human.     

Mycobacterium kansasii in a rhesus monkey

The incidence of pulmonary disease caused by "atypical" mycobacteria has been increasing gradually in the human population since the 1950s. Mycobacterium kansasii and Mycobacterium intracellulare are the two organisms most responsible for this trend. A rhesus monkey was euthanatized and necropsied after reacting positive to mammalian Old Tuberculin on semi-annual testing. Histopathology demonstrated the presence of small numbers of acid fast organisms in pulmonary lesions. Further microbiological testing identified the causative organism as M. kansasii.