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Biomedical subjects

D C Johnson

Publications and source records attributed to D C Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1987

Opposite effect of human chorionic gonadotropin on placental and ovarian synthesis of androstenedione.

In the present studies, we have investigated the role of human chorionic gonadotropin on the biosynthesis of androgens by placentas and corpora lutea of the pregnant rat. We first sought to compare the effect of hCG on placental and ovarian secretion of androstenedione in vivo. For this purpose either 1.5 IU hCG or vehicle was administered to pregnant rats twice on days 12 and 13 and once on the morning of day 14. Blood was obtained from either the ovarian or the uterine vein. After hCG administration, levels of androstenedione secreted in the ovarian vein increased dramatically, whereas those in the uterine vein declined significantly. To establish that changes in androgen levels in the uterine and ovarian veins are due to changes in biosynthetic activity and also to compare the action of hCG on placentas and corpora lutea, tissues were dissected out from rats treated with 0, 1.5, or 9 IU hCG twice daily and incubated in vitro. hCG administration increased the capacity of luteal cells to synthesize androstenedione de novo by approximately 100% and concomitantly decreased placental secretion of androstenedione by approximately 75%. Addition of high density lipoprotein to the medium enhanced both basal and hCG-stimulated androstenedione production by luteal tissues but had no effect on either basal or hCG-inhibited androstenedione biosynthesis by the placenta. To determine which step in the placental biosynthesis of androstenedione is inhibited by increased levels of LH, we determined the effect of hCG administration, on cholesterol biosynthesis and storage, synthesis of progesterone substrate, and the activities of 17 alpha-hydroxylase/17,20-lyase. hCG did not affect the activities of the rate limiting cholesterogenic enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, placental content of cholesterol and cholesteryl ester, or the placental production of progesterone. However, hCG did cause a substantial decrease in the activity of 17 alpha-hydroxylase/17,20-lyase enzyme(s); responsible for the conversion of progesterone to androgen. In summary, results of the present investigation demonstrate that increases in LH activity in the circulation act on two different steroidogenic glands to either enhance or reduce androgen biosynthesis. hCG stimulates luteal secretion of androstenedione and simultaneously inhibits placental production of this steroid.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldehyde-Lyases↗
PubMed1987

Selective stimulation of luteal androgen biosynthesis by luteinizing hormone: comparison of hormonal regulation of P45017 alpha activity in corpora lutea and follicles.

Recent investigations have indicated that luteal cells of pregnant rats become capable of synthesizing androgen and estradiol when stimulated by sustained low levels of LH/hCG. In this investigation we sought 1) to determine whether hCG causes the induction/activation of the luteal enzymes responsible for the conversion of progesterone to estradiol, 2) to investigate the time course of hCG action, and 3) to compare the effect of hCG on luteal and follicular P45017 alpha activities. To determine first the minimum stimulatory dose of hCG, pregnant rats were treated with 0, 1.5, 3, 9, or 30 IU hCG twice on days 12 and 13 and once on day 14. Two hours after the last injection, rats were bled from the ovarian vein, and corpora lutea were isolated and incubated for the determination of in vitro steroid production. Exposure of rats to twice daily injections of 1.5 IU hCG caused a dramatic increase in the ovarian secretion and luteal production of both testosterone and estradiol. However, an inverse dose-related response was observed with higher doses of hCG. To determine the time course of hCG action, pregnant rats were injected with a single dose of 3 IU hCG, and steroid production was determined at different times thereafter. There was no increase in either in vivo or in vitro testosterone and estradiol production until 12 h after hCG administration, at which time a dramatic increase in the secretion of both steroids was observed. hCG administration did not affect the capacity of luteal cells to secrete progesterone, nor did it enhance aromatase activity. It did, however, increase P45017 alpha activities; lyase and hydroxylase activities were stimulated 5- and 1.7-fold, respectively. To compare the effects of hCG on luteal and follicular P45017 alpha, both corpora lutea and follicles were isolated from ovaries of pregnant rats treated with either 1.5 IU hCG or vehicle between days 12-14. In vivo hCG administration caused at least a 1000-fold increase in the specific activity of follicular 17 alpha-hydroxylase and 17,20-lyase. The hCG-induced increase in the specific activities of both hydroxylase and lyase in the follicle far exceeded that in the corpora lutea. However, total lyase and hydroxylase activities in each follicle were only 3- and 5.5-fold higher, respectively, than those in the corpus luteum. In summary, the results of the present investigation have revealed that hCG stimulation of luteal estradiol production is due to a selective effect of this gonadotropin on P45017 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1987

Adrenal gland modulates oestrogen requirement for implantation in the rat.

The effect of adrenal steroids upon implantation was evaluated by examining the efficacy of oestradiol-17 beta on the initiation of implantation in ovariectomized, ovariectomized plus adrenalectomized or hypophysectomized pregnant rats treated with progesterone. More oestrogen (X 5) was required in ovariectomized animals to obtain results equivalent to those obtained with the other animal models.

Adrenal Glands↗
PubMed1987

2-Fluoro-oestradiol does not cause uterine refractoriness but inhibits oestradiol-induced implantation in rats.

An intravenous injection of 2-fluoro-oestradiol simultaneously with an implantation-inducing dose of oestradiol reduced the number of implantation sites in delayed implanting hypophysectomized rats maintained with progesterone. Administration of 2-fluoro-oestradiol 1 h before or after oestradiol had no effect. Furthermore, injection of as much as 500 ng 2-fluoro-oestradiol 48 h before administration of oestradiol failed to have any effect upon implantation, i.e. failure to block implantation was correlated with failure to induce the uterine refractory state. These results suggest that conversion of primary oestrogens to catechol oestrogens could be important for implantation as well as for the induction of the oestrogen refractory state in the uterus.

Animals↗
PubMed1987

Quantitative changes in ovarian 17 alpha-hydroxylase/C17,20-lyase and aromatase activities during the estrous cycle of the hamster.

Aromatase activity of the microsomal fraction of ovarian homogenates, measured by a tritium exchange assay using androstenedione (A-dione) as substrate, did not change during the 4-day estrous cycle of the hamster. In contrast, 17 alpha-hydroxylase, measured by a tritium exchange assay with progesterone as substrate, and particularly C17,20-lyase activity, evaluated by acetic acid production from progesterone, drastically decreased on the afternoon of proestrus (Day 4). The latter two activities remained low on Days 1 and 2 but increased dramatically on Day 3 and the morning of Day 4. The serum concentration of A-dione and 17-hydroxyprogesterone reached a peak at 1600 hr of proestrus and then decreased rapidly as the enzyme activities decreased. A-dione levels were undetectable on Day 1 but 17-hydroxyprogesterone levels remained elevated through Day 2. The results are consistent with the view that 17 alpha-hydroxylase and C17,20-lyase are activities of a single cytochrome P-450, as has been shown for testis and adrenal. Increases in hydroxylase and lyase activities occur concomitantly with decreases in the serum concentrations of progesterone, suggesting that the latter steroid may play a role in controlling these enzymes.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Aorta-coronary bypass grafting with polytetrafluoroethylene conduits. Early and late outcome in eight patients.

During 1982 and 1983 we performed aorta-coronary bypass grafts on eight patients using 4 mm polytetrafluoroethylene conduits and predominantly the multiple sequential graft technique. Angiography was performed 1 week postoperatively and seven of eight patients had patent grafts and were angina free. At 1 year's follow-up 18 of 28 distal anastomoses were patent and five of eight patients were angina free. At 45 month's follow-up four of 28 distal anastomoses were patent and one of eight patients was angina free.

Angina Pectoris↗
PubMed1987

Surgical therapy for supraventricular tachycardia, a potentially curable disorder.

One hundred fifty-six patients underwent investigation and operation for supraventricular tachycardia: 145 had attempts at curative operations and 11 had His bundle section. Operative mortality was 0.68% and there were no late deaths among patients having curative operations. One patient died suddenly 1 year after His bundle section. All patients underwent electrophysiologic study before discharge and 6 months postoperatively. A satisfactory result, without supraventricular tachycardia and without medication, was achieved in 96.5% of all patients. Ninety-three percent have no supraventricular tachycardia and no demonstrable reentrant pathway at electrophysiologic study. All free wall accessory atrioventricular connections were divided and 97.7% of the patients were cured. Ninety percent of patients with posterior septal accessory atrioventricular connections had a satisfactory result, with cure demonstrated at late electrophysiologic study in 84%. Fifteen patients with atrioventricular junctional reentrant tachycardia were all cured, with preservation of normal atrioventricular conduction. Eight (88%) of nine patients with right atrial tachycardia were cured, and two patients with nodoventricular fibers and one patient with incessant atrioventricular junctional tachycardia had satisfactory results. Supraventricular tachycardia is now a potentially curable disorder when managed by low risk surgical procedures that offer a high cure rate.

Adolescent↗
PubMed1986

Endocrine studies in a male patient with choriocarcinoma and gynecomastia.

Sex hormone profiles were studied in serum and tumor extracts of a man with pulmonary choriocarcinoma and gynecomastia. Although levels of serum estrogens were elevated as expected, serum androgen levels were uncharacteristically quite high. Tumor extract contained increased quantities of both androgens and estrogens when compared with surrounding normal lung tissue, but lacked the enzymes necessary for androgen biosynthesis while retaining aromatase activity. It is concluded that unlike the usual male patient with choriocarcinoma, the tumor-derived beta-human chorionic gonadotropin stimulated testicular androgen production. These androgens were in turn concentrated by the tumor and converted in part to estrogens. Furthermore, gynecomastia can occur even in the face of high serum androgen concentrations provided total estrogen levels are also disproportionately elevated.

Adult↗
PubMed1986

Marijuana smoking as cause of reduction in single-breath carbon monoxide diffusing capacity.

To investigate the effects of chronic marijuana smoking on lung function, pulmonary function tests including single-breath carbon monoxide diffusing capacities were performed in 15 healthy women who smoked 1.7 +/- 1.4 (mean +/- SD) marijuana cigarettes per day for 235 +/- 135 days per year for a mean of 10.5 +/- 3.7 years. Control groups included 27 nonsmoking and 26 tobacco-smoking women. Results revealed that marijuana smoking with or without tobacco is associated with a reduction in the single-breath carbon monoxide diffusing capacity to 74 +/- 20 percent of predicted, which was significantly different from that in the nonsmoking control subjects (92 +/- 11 percent; p less than 0.05). The subset of subjects who smoked marijuana and tobacco had a further reduction of the single-breath carbon monoxide diffusing capacity to 65 +/- 17 percent, which was significantly different from that in both nonsmoking and smoking control subjects (80 +/- 7 percent). These results suggest that heavy marijuana smoking when added to tobacco smoking may damage the gas exchange surface of the lung.

Adult↗
PubMed1986

Relationship between in vivo and in vitro 17 alpha-hydroxylase and C17,20-lyase activity in ovaries of immature hypophysectomized rats treated chronically with human chorionic gonadotropin.

The production of 3H2O from 17 alpha-3H-progesterone and 14CH3COOH from [21-14C]progesterone were used to measure the 17 alpha-hydroxylase and C17,20-lyase activities respectively in the microsomal + mitochondrial fraction of homogenates of ovaries from immature hypophysectomized rats chronically treated with human chorionic gonadotropin (hCG). The highly stimulated thecal and interstitial tissues were considered the only source of enzyme. hCG produced an increase in 17-hydroxyprogesterone, and androstenedione, but a drastic decrease in enzyme activity within 6 h; this could be largely prevented by pretreatment of the rats with cycloheximide or aminoglutethimide but actinomycin D was ineffective. After a nadir at 24 h, enzyme activities increased to more than double those of the starting level; this could be prevented by cycloheximide. Maximal activity levels were greatly decreased by cycloheximide and modestly increased by aminoglutethimide. Cessation of treatment at 60 h followed by a single injection of hCG 24 h later did not cause a loss, but delays of 36 or more hours produced a dramatic decrease in enzyme activity, which could be prevented by aminoglutethimide. The results indicate that the level of activity of these enzymes attained in the ovary following exposure to hCG is determined by a balance between the amount of substrate provided and production of enzyme and/or stimulating factors. Therefore, maintenance of increased enzyme activity induced by gonadotropin appears to be under genomic control.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Scanning fluorescence correlation spectroscopy. II. Application to virus glycoprotein aggregation.

Scanning fluorescence correlation spectroscopy is a new approach to measuring changes in the state of aggregation of cell membrane proteins. Measurements of the mean number of aggregates of virus glycoproteins from Sindbis virus and vesicular stomatitis virus agree with the findings of a recent fluorescence photobleaching recovery study on the same systems (Johnson, D.C., M.J. Schlesinger, and E.L. Elson, 1981, Cell, 23:423-431). Sindbis Virus glycoproteins are immobilized and cannot be induced to aggregate further by antibody cross linking. In this study, we find that Sindbis virus glycoprotein is more highly aggregated than vesicular stomatitis virus glycoprotein, which can be patched further with antibody. These measurements demonstrate the potential of scanning fluorescence correlation spectroscopy in studies of aggregation problems in membranes of cultured cells.

Animals↗
PubMed1986

Pathogenicity in mice of herpes simplex virus type 2 mutants unable to express glycoprotein C.

Herpes simplex virus type 2 (HSV-2) mutants that were unable to express glycoprotein C (gC-2) were isolated. Deletions were made in a cloned copy of the gC-2 gene, and recombinant viruses containing these deletions were screened by using an immunoreactive plaque selection protocol. The viruses did not display a syncytial phenotype. Intravaginal inoculation of BALB/cJ mice with one of the HSV-2 gC-2- viruses produced local inflammation followed by a lethal spread of the viral infection into the nervous system in a manner identical to that produced by parental HSV-2 strain 333. Similarly, intracerebral inoculation of DBA-2 mice with the gC-2- virus produced a lethal neurological disease paralleling that caused by HSV-2 strain 333. These results indicate that gC-2 is not required for the spread of HSV-2 infections in mice.

Animals↗
PubMed1986

Placental secretion of androgens in the rat.

In contrast to the human placenta, which does not secrete androgens, the rat placenta synthesizes significant amounts of these steroids. The purpose of this study was to determine why the rat placenta does not secrete androgens before day 12 of pregnancy, to ascertain whether the rat placenta secretes more androstenedione than testosterone, to compare the capacity of luteal and placental tissue to secrete androgen, and to determine whether the rat placental produces androstenedione via the delta 4- or delta 5-steroidogenic pathway. To determine whether the inability of the rat placenta to produce androstenedione before midpregnancy was due to the absence of active 17 alpha-hydroxylase and 17,20-lyase enzymes and also to investigate the ontogeny of both placental production of androstenedione and enzyme activities, placentas were isolated from rats between days 8-21 of pregnancy and either incubated or used to determine the activities of 17 alpha-hydroxylase and 17,20-lyase. Before day 11, enzyme activity was not detectable. From day 11, both enzyme activities and placental secretion of androstenedione steadily increased to peak values by day 18 and declined just before parturition. To investigate the principal aromatizable androgen secreted both in vivo and in vitro approaches were used. Levels of androstenedione and testosterone found in the uterine vein as well as those produced by placental tissue were determined. Rat placentas secreted markedly more androstenedione than testosterone, both in vivo and in vitro. When placental and luteal secretion of androstenedione and testosterone were compared, it was found that luteal tissue had a higher capacity for androgen synthesis than did the placenta. Yet, because of its greater mass, each placenta secreted 15 times more androstenedione and 4.5 times more testosterone than each corpus luteum. To determine the preferential usage of progesterone or pregnenolone as substrate by the placenta, [14C] progesterone and [3H]pregnenolone were added in equimolar concentrations. The resulting 14C to 3H ratio of the androgen produced indicates that the preferred substrate is progesterone. In summary, results of this investigation describe, for the first time, the development of 17 alpha-hydroxylase and 17,20-lyase activities in the rat placenta and demonstrate that the placenta does not produce androgen before day 11 due to the absence of active enzymes. The results further demonstrate that the rat placenta secretes significantly more androstenedione that testosterone both in vivo and in vitro, produces more androgen than the corpus luteum because of its greater mass, and forms its androgen primarily via the delta 4-st

Aldehyde-Lyases↗
PubMed1986

Estrogens with reduced catechol-forming capacity fail to induce implantation in the rat.

Catechol estradiol can induce implantation of the embryo in a progesterone-primed uterus, but we do not know whether conversion of estrogen to a catechol is essential for implantation. The present study examined the ability of fluorinated estradiols that have a reduced capability of catechol formation to induce implantation. Delayed implantation in rats that were hypophysectomized on the third day postcoitum was maintained by daily injection of progesterone. On the fifth day of progesterone treatment they were injected intravenously with estradiol-17 beta (E2), or various doses of 2-fluoroestradiol-17 beta (2-F1-E2) or 4-fluoroestradiol-17 beta (4-F1-E2) and examined 24 hr later for evidence of initiation of implantation. All animals treated with 25 ng of E2 showed normal numbers of implantation sites, as did those receiving 60 ng of 4-F1-E2. In contrast, 2-F1-E2 failed to initiate implantation with doses as high as 300 ng per animal; there were only single sites in two of eight rats treated with 500 ng. Initiation of implantation was not correlated with lack of uterotropic estrogenicity. The results suggest that formation of catechol estrogen may be an important step in mediating estrogen function for implantation of the embryo.

Animals↗