Increased activity of ovarian thecal cytochrome P45017α in the hamster induced by endogenous LH

1989 ◽  
Vol 121 (3) ◽  
pp. 374-382 ◽  
Author(s):  
Donald C. Johnson ◽  
Mitra Sen

Abstract. The in vivo regulatory action of LH on the ovarian androgen synthesizing enzyme cytochrome P45017α (17α-hydroxylase/C17, 20-lyase) was studied in cyclic golden hamsters. Immunohistochemical studies using anti-porcine testicular cytochrome P45017α antibody indicated that the enzyme was limited to thecal cells. Transient removal of the negative feedback action of endogenous steroids by use of aminoglutethimide phosphate produced an increase in endogenous gonadotropins. A single dose (30 mg) of aminoglutethimide on days 1, 2 or 3 of the estrous cycle (day 1 = estrus), increased serum levels of LH, but only for about 12 h. Increases in enzyme activities, which persisted for at least 24 h, followed. Two doses of aminoglutethimide, 12 h apart, maintained elevated levels of serum LH for about 36 h, and enzyme activites for at least 48 h. However, when the drug was given after the pre-ovulatory surge of LH on proestrus, and again on the morning of estrus, neither serum LH nor enzyme activity levels increased within 24 h. Induced increases in enzyme activity had no effect upon ovulation rate, as determined by the number of oviductal eggs present on the morning of estrus. The results demonstrate clearly a close correlation between serum concentrations of LH and ovarian androgen synthesizing enzyme activity.

1979 ◽  
Vol 46 (2) ◽  
pp. 334-339 ◽  
Author(s):  
R. W. Hubbard ◽  
R. E. Criss ◽  
L. P. Elliott ◽  
C. Kelly ◽  
W. T. Matthew ◽  
...  

A total of 171 untrained, unacclimatized, and unanesthetized rats were either exercised to exhaustion at one of four ambient temperatures (5, 20, 26, or 30 degrees C), or were restrained and heated at an ambient temperature of 41.5 degrees C until their core temperatures reached a preselected end point between 41.0 and 43.3 degrees C. The serum levels of creatine phosphokinase (CRK) and two transaminases (SGOT and SGPT) were determined at 30 min, 24, 48, 72, and 96 h posttreatment. Peak enzyme activity for CPK was noted primarily at the 30-min sampling period and at 24 h for the transaminases. The data indicated that under these conditions a) the transaminase SGOT was elevated in the serum as a consequence of the extent and duration of prior hyperthermia, b) the transaminase SGOT was released in moderate amounts after exhaustive exercise but reached its greatest activity levels following hyperthermia, and c) the activity of CPK was increased by the duration of exhaustive exercise and was less sensitive than either transaminase to prior hyperthermia. As a result, each of the three experimental conditions: a) exercise without hyperthermia, b) exercise with hyperthermia, and c) sedentary hyperthermia, produced a unique pattern of serum enzyme activity that would appear useful in diagnosing a variety of heat- and/or work-induced disorders.


1981 ◽  
Vol 241 (3) ◽  
pp. E221-E225 ◽  
Author(s):  
K. Taya ◽  
G. S. Greenwald

Thirty-day-old rats given a single subcutaneous injection of 5 IU pregnant mare serum gonadotropin (PMS) at 0900 h ovulated on the morning of day 33 (= estrus). However, the second ovulation did not occur until 9.4 days later. To determine the mechanism responsible for the delay in the second ovulation, in vivo and in vitro determinations of steroid and peptide hormones were compared between PMS-primed immature rats and adult cyclic rats. In PMS-primed rats, the corpora lutea (CL) produced progesterone for 2 days longer (until day 36) than the CL of the adult rat. Serum levels of 20 alpha-dihydroprogesterone, testosterone, and estradiol in PMS-primed rats were significantly lower than the corresponding values in adult rats. Serum LH was consistently lower in the PMS-primed rats. An increase in serum FSH occurred on days 36–37, which may be responsible for maturation of the follicles destined to ovulate at the second ovulation. On day 37, the nonluteal ovary of the PMS-primed rats also began to produce in vitro appreciable amounts of testosterone and estradiol. These findings suggest that the greater levels of prolactin and/or low levels of luteinizing hormone during estrus in PMS-primed rats may be responsible for the prolonged secretion of progesterone by the CL. This in turn inhibits follicular maturation, indirectly by lowering serum LH, which is reflected in reduced ability of the follicles in vitro to produce testosterone and estradiol until the CL regress.


2000 ◽  
Vol 68 (1) ◽  
pp. 335-341 ◽  
Author(s):  
Aharona Glatman-Freedman ◽  
Aron J. Mednick ◽  
Nikoletta Lendvai ◽  
Arturo Casadevall

ABSTRACT Lipoarabinomannan (LAM) is a component of the mycobacterial surface which has been associated with a variety of deleterious effects on immune system function. Despite the importance of LAM to the pathogenesis of mycobacterial infection, there is no information available on its fate in vivo. In this study, we determined the pharmacokinetics and tissue distribution of exogenously administered LAM in mice. For measurements of serum and tissue LAM concentrations, we developed an enzyme-linked immunosorbent assay which used monoclonal antibodies of different isotypes to capture and detect LAM at concentrations of ≥0.4 μg/ml. Intravenous administration of LAM to mice resulted in transient serum levels with organ deposition in the spleen and in the liver. Immunohistochemical studies localized LAM to the spleen marginal zone macrophages and, to a lesser degree, to liver macrophages. When LAM was administered to mice previously given a LAM-binding immunoglobulin M (IgM), LAM was very rapidly cleared from circulation. In those mice, deposition of LAM in the spleen was significantly reduced while LAM deposition in the liver increased. Administration of LAM-binding IgM resulted in significant levels of IgM to LAM in bile consistent with an increased hepatobiliary excretion of LAM in the presence of specific antibody. Bile, liver extracts, and bile salts were found to rapidly inactivate the immunoreactivity of LAM. The results indicate that serum clearance and organ deposition of LAM in mice are affected by the presence of LAM-binding antibody and suggest a mechanism by which antibody could modify the course of mycobacterial infection.


1990 ◽  
Vol 68 (2) ◽  
pp. 513-519 ◽  
Author(s):  
K. J. Rodnick ◽  
C. E. Mondon ◽  
W. L. Haskell ◽  
S. Azhar ◽  
G. M. Reaven

To evaluate the relationship between enhanced insulin action and level of exercise training, in vivo glucose uptake was assessed in the absence of added insulin and during insulin-stimulated conditions for three activity levels of voluntarily trained rats (low 2-5 km/day, medium 6-9 km/day, high 11-16 km/day). After rats rested for 24 h and fasted overnight, glucose uptake was estimated by comparing steady-state serum glucose (SSSG) levels at low insulin (SSSI) concentrations achieved during an insulin suppression test. In the absence of added insulin, SSSI averaged approximately 20 microU/ml and glucose uptake was similar for high runners and younger weight-matched controls. However, with insulin added to sustain SSSI at approximately 35 microU/ml, SSSG was significantly reduced in all runners (P less than 0.02), with the lowest value attained in high runners. Fasting serum triglycerides were also reduced in all runners (P less than 0.05), with the lowest values seen in medium and high runners. The concentration of glycogen in liver and select skeletal muscles at the start of the study was not different between trained and control rats, suggesting that enhanced insulin-stimulated glucose uptake was not the result of lower glycogen levels. In addition, glycogen synthase and succinate dehydrogenase activities in biceps femoris muscle were only elevated for high runners, but glycogen synthase activity was not enhanced in plantaris muscle and was decreased in soleus muscle. These findings indicate that enhanced insulin-stimulated glucose uptake and reduced serum triglyceride concentrations induced in exercise-trained rats at varying activity levels are dissociated from changes in glycogen synthase and oxidative enzyme activity for skeletal muscle.


2013 ◽  
Vol 79 (18) ◽  
pp. 5480-5487 ◽  
Author(s):  
A. J. Hunter ◽  
T. A. Morris ◽  
B. Jin ◽  
C. P. Saint ◽  
J. M. Kelly

ABSTRACTAspergillus oryzaehas been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of anAspergillus nidulansstrain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show thatAspergillus oryzaecontains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in bothAspergillus nidulansandAspergillus oryzaeare mirrored at the transcript level, indicating transcriptional regulation. We report thatAspergillus oryzaeDAR3699, originally isolated from soy fermentation, has a similar phenotype to that of acreBdeletion mutant of the RIB40 strain, and it contains a mutation in thecreBgene. Collectively, the results forAspergillus oryzae,Aspergillus nidulans,Trichoderma reesei, andPenicillium decumbensshow that deletion ofcreBmay be broadly useful in diverse fungi for increasing production of a variety of enzymes.


1995 ◽  
Vol 145 (1) ◽  
pp. 59-67 ◽  
Author(s):  
D C Johnson ◽  
L H Crane

Abstract A study was designed to compare the effects of exogenous and endogenous oestrogens upon the expression of steroid 17α-hydroxylase/C17,20-lyase (CYP17) in the immature hypophysectomized rat ovary. C17,20-lyase activity was measured ex vivo using [21-14C]progesterone, while serum concentrations of androstenedione indicated in vivo activity. Immunocytochemistry was used to localize the enzyme within the ovary. Activity of CYP17 increased dramatically and remained high in thecal and interstitial cells after injection of equine chorionic gonadotrophin, even though serum oestradiol (OE2) levels exceeded 2 nmol/l. Production of comparable serum levels by the use of Silastic capsules containing OE2 greatly suppressed but did not stop, expression of the enzyme induced by repeated doses of human chorionic gonadotrophin (hCG). Subcutaneous implantation of Silastic capsules (1 cm) containing diethylstilboestrol (DES) stimulated follicular growth and increased ovarian weight by 67%, 5 days later. Injection of 50 IU hCG at various times after removal of the implant produced time-dependent changes in CYP17 activity and serum androstenedione levels, when measured 30 h later. Although the initial effect of removal of DES was an increase in CYP17 activity, delaying injection of hCG resulted in a reduced response. The results indicated that: (1) endogenous oestrogens do not inhibit CYP17 expression; (2) exogenous oestrogens only reduce the number of thecal/interstitial cells expressing CYP17 when they are exposed to hCG; (3) pretreatment with oestrogen removes the ovarian interstitial but not the thecal cell expression of CYP17 in response to hCG; and (4) oestrogens can be stimulatory for CYP17 expression in thecal cells. Journal of Endocrinology (1995) 145, 59–67


2021 ◽  
Vol 23 ◽  
Author(s):  
Ogochukwu Amaeze ◽  
Emily S. Marques ◽  
Wei Wei ◽  
Sarah Lazzaro ◽  
Nathaniel Johnson ◽  
...  

Background: Herbal medicine represents a significant component of disease prevention and therapy in most African countries. Herb-drug interactions (HDI) can arise from the co-administration of herbal and orthodox medicines. Objective: This study assessed the potential for HDI of V. amygdalina, O. gratissimum, M. oleifera, A. indica, and P. nitida extracts using in vitro assays. Little is known about these medicinal plants' potential for drug interaction despite their extensive use in Nigeria for several disease conditions. Method: The medicinal plant crude extracts were evaluated for Cytochrome P450 (CYP) enzyme induction using cryopreserved human hepatocytes. Enzyme activity was determined by quantifying probe substrate metabolism and metabolite formation using liquid chromatography-mass spectrometry/mass spectrometry. The extracts were evaluated for the potential to inhibit P-glycoprotein (P-gp) activity using human embryonic kidney membrane vesicles over-expressing human P-gp. The herbal extracts in vivo drug interaction potential was predicted based on the USFDA drug interaction guidance. Result: O. gratissimum and P. nitida methanol extracts induced CYP1A2 enzyme activity by greater than 3-fold. P. nitida methanol extracts showed over 2-fold induction of CYP1A2 mRNA expression. O. gratissimum methanol extract induced CYP2B6 mRNA expression over 2-fold. P. nitida and A. indica methanol extracts showed potent inhibition of P-gp activity (IC50: 3.8 and 5.4 µg/mL), respectively, while V. amygdalina and M. oleifera methanol extracts showed moderate P-gp inhibition (IC50: 12.1 and 37.2 µg/mL, respectively). Conclusion: Our studies suggested that the medicinal plants’ extracts can modulate CYP enzymes and P-gp activity with the potential to cause herb-drug interaction in vivo.


1977 ◽  
Vol 145 (4) ◽  
pp. 1054-1059 ◽  
Author(s):  
M D Maines ◽  
J Cohn

Skin heme oxygenase is locally elevated by stimuli such as tissue injury and injections of whole blood, myoglobin, and hematin. The enzyme activity is also increased at the proximity of the injection site of chemicals such as cobalt and cobalt-protoporphyrin-IX (cobalt-heme). Protoporphyrin-IX, the tetrapyrrole nucleus of type-b heme compounds, was ineffective in altering the enzyme activity in vivo. The developmental pattern of heme oxygenase in skin was compared to that of the enzyme in liver. The enzyme activity in both organs was greatest during the 1st postpartum wk and declined to adult levels after 2 wk. The physiological implications of the increased activity of skin heme oxygenase are discussed, and it is concluded that the activity of the hepatic heme oxygenase system and that of the skin are regulated by the same mechanism.


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