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Biomedical subjects

S Honma

Publications and source records attributed to S Honma.

At least 253 records · Page 14Linked to original sources

[The in vivo metabolism of chlormadinone acetate in guinea pig and the uptake of testosterone-3 H and chlormadinone acetate-3 H in prostate of castrated male rat (author's transl)].

The metabolic fate and distribution of the anti-androgenic agent, 17 alpha-acetoxy-6-chloropregna-4, 6-diene-3, 20-dione (chlormadinone acetate, CMA), was investigated using guinea-pigs and rats. In order to elucidate the metabolic outcome, chlormadinone acetate was labelled with 3H at position C-1 and with deuterium at methyl moiety of the 17alpha-acetate. Guineapigs were maintained for 7 days on a diet containing 1% chlormadinone acetate having a ratio of d2/d0=1 and then for 1 day on a diet containing 1% chlormadinone acetate having radioactivity. The isolation and purification of the urinary and fecal metabolites were usually carried out in the manner shown in Fig. 1 and 2. The metabolites identified were as follows: the parent drug, monohydroxychlormadinone acetate having the additional hydroxy function in the steroid skeleton, 15 beta-hydroxy, 2 alpha-, 2 beta-hydroxy and unknown position, dihydroxy chlormadinone acetate, 2 alpha-, 3 beta-dihydroxy, 2 alpha-, 3 alpha-dihydroxychlormadinone acetate. Further, three dechlornated and reduced metabolites were also isolated from urine and feces. These were 17 a-acetoxy-5a-pregnane-3 beta-ol-20-one and its isomer, and 17-acetoxy-5 beta-pregnane-2 beta, 3 beta, 15a-triol-20-one. But 3 beta-hydroxychlormadinone acetate possessd with anti-androgenic activity, one of the main metabolites in humans and rats, was not found in the excreta of the guinea-pigs. However, the main metabolite on the prostate of the guinea-pigs and rats and 3 beta-hydroxychlormadinone acetate. Chlormadinone acetate causes regression of the seminal vesicle and prostate in oral administration to a mammalian. It was therefore hypothesized that chlormadinone acetate might inhibit the uptake and retention of testosterone in these tissues. To elucidate this hypothesis, the accumulation of testosterone-3H and chlormadinone acetate-3H in several organs was determined on castrated rats and normal rats, respectively. When 1.0 muM of testosterone-3H was given to the castrated rats, a maximal accumulation of radioactivity resulted in seminal vesicle and prostate at 15 approximately 120 min. While the treatment of chlormadinone acetate significantly prevented the accumulation of testosterone-3H in the seminal vesicle and prostate, but levels in fat and muscle were not evident. In addition, to prove the accumulation of chlormadinone acetate in androgen target tissues, 3 muM of chlormadinone acetate-3H was similarly administered to castrated rats. The uptake of chlormadinone acetate on the target organs was higher than that in normal rats at 5 approximately 30 min.

Animals↗

Age- and sex-related changes of peritoneal free cells in mice: quantitative morphologic study.

Peritoneal free cells in 256 mice of either sex ranging in age from 1 to 120 days were studied by quantitative morphologic procedures. The total number of peritoneal free cells examined by Coulter counter increased with age. After 40 days the increase was more marked in females than in males, so that a significant sex difference appeared in the number of peritoneal cells after puberty. The size distribution curves of peritoneal free cells obtained by a Coulter counter and channelyzer indicated that, irrespective of age and sex, peritoneal cells are composed of three populations which are each different in cell size. By light microscopy, the three components of peritoneal cells corresponded to small lymphocytes(type I cells), medium-sized mononuclear cells (type II cells), and macrophages (type II cells). In newborn mice, type III cells were about 80% of peritoneal free cells, and type I and II cells were less than 2%. Type I cells increased slowly in number with age, and they remained smallest in number at any age. Type II cells increased rapidly with age, and they were most numerous after puberty. Moreover, type II cells were significantly more numerous in females than in males. The sex difference of type II cells accounts for that in the total number of peritoneal cells. Type III cells also increased in number wtih age until puberty. After puberty they remained almost unchanged in number. The sex difference in the total number of peritoneal free cells and the number of type II cells was considered to be caused primarily by the testis but not by the ovary.

Age Factors↗

Response of peritoneal cells to horseradish peroxidase and aldehyde-fixed erythrocytes in the mouse: an electron microscope study.

In adult dd-mice, response of peritoneal free cells to either horseradish peroxidase (HRP) or glutaraldehyde-fixed erythrocytes were examined by electron microscopy. As reported previously (ABE et al., 1979), peritoneal free cells are classified into three types: type I, II and III cells. Type I cells are small lymphocytes, type II cells are medium-sized mononuclear cells, and type III cells are macrophages. The amount of HRP taken up is very large in type III cells. The cells contain numerous vacuoles filled with HRP. Type I and II cells also have vesicles containing HRP. The vesicles are fewer in type I cells than in type II. Type III cells rapidly enclose erythrocytes by thin cytoplasmic flaps and then ingest several erythrocytes. In type III cells, a labyrinth of ramifying tubes seen in the peripheral cytoplasm may serve as a reserve of the membrane system for allowing a rapid coverage and internalization of large foreign materials. A part of type II cells attach to erythrocytes and take them by a varying depth of invagination. Type I cells do not respond to erythrocytes at all. In conclusion, the three types of peritoneal cells can be differentiated by their response to foreign materials as well as by their cytologic features.

Aldehydes↗

Pubertal manifestation of sex difference in circadian rhythm of corticotrophin-releasing activity in the rat hypothalamus.

Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.

Age Factors↗

[Sex difference in the circadian rhythm of corticotropin-releasing activity in the rat hypothalamus (author's transl)].

Sex difference in the circadian rhythm of the hypothalamic content of Corticotropin-Releasing Factor (CRF) and plasma corticosterone levels was examined in the rat. In the male rat the CRF content was higher in the afternoon than in the morning. In contrast, the hypothalamic CRF content in the female rat was higher in the morning. The peak value was found at 8 a.m. and it fell rapidly around noon with a concomitant sharp rise in the plasma corticosterone. Thus, the whole pattern of CRF content during a 24-hour period makes a mirror image of that of plasma corticosterone. The influence of gonadal hormones on the sex difference was then examined by following variations in the CRF content after ovariectomy. Even after chronic ovariectomy, essential features of the female pattern of CRF rhythm persisted: rapid fall of the CRF content was accompanied by a sharp rise in the plasma corticosterone level. It is noteworthy however that ovariectomy reduced the morning level of CRF activity without elevating the afternoon level, resulting in a peak shift toward noon. The female pattern of CRF rhythmpersisted similarly after bilateral ganglionectomy which is known to affect the biogenic amine rhythm in the pineal gland. The persistence of the female pattern may suggest some endogenous nature of the rhythm. It was then possibly that sex differentiation in the central nervous system (CNS) might be related with manifestation of the female pattern. In order to elucidate this point, postnatal development of circadian rhythm of CRF activity was examined in male and female rats separately. It was found that the CRF rhythm became manifest both in male and female rats around the third week of postnatal life and there was no essential difference in their rhythm pattern. In other words, both male and female rats begin their CRF rhythm with so-called male pattern, with higher values in the afternoon than in the end of the third week of life. In contrast, the CRF rhythm in females rats showed a marked change at ages of five to six weeks during which the onset of puberty intervened in our series of experiment;during this period, the CRF rhythm in female rats turned into the so-called female pattern, with higher values of CRF activity in the morning than in the afternoon. It was of interest that a marked rise in the plasma corticosterone, characteristic of mature female rats, concomitantly appeared. Further attempt were made to examine the effect of gonadal hormones in the periratal period. The hypothalamic CRF content in androgen sterilized female rats as well as in neonatally castrated male rats showed no circadian rhythm. The results implicate subtleness of hormonal effect in simulating physiological processes. In fact, CRF rhythms are variable depending on stages of the estrous cycle: during proestrus and estrus, the CRF content was markedly higher in the morning (9 a.m.) than in the afternoon (4 p.m.). But no significant difference was observed between them during diestrus I and II...

Age Factors↗