THE SECRETION, INTERCONVERSION AND CATABOLISM OF CORTISOL, CORTISONE AND SOME OF THEIR METABOLITES IN MAN

1969 ◽  
Vol 62 (2) ◽  
pp. 339-359 ◽  
Author(s):  
E. Bailey ◽  
H. F. West

ABSTRACT Trace doses of one or more of the following radioactive steroids were given to 2 normal and 4 rheumatoid arthritic men: cortisol, cortisone, 20α-dihydrocortisol, 20β-dihydrocortisol and tetrahydrocortisol. The specific activities of the given steroids and some of their unconjugated and conjugated metabolites in urine were measured. The secretion rates of cortisol and cortisone for the 2 normal men, deduced from their specific activities in urine, were found to be approximately equal and in sum approximately equal to the secretion rate of cortisol deduced from the specific activities of their conjugated metabolites. Evidence of the speed of interconversion of cortisol and cortisone was obtained by giving [4-14C] cortisol and [1,2-3H] cortisone simultaneously to the 2 normal subjects and measuring the specific activities of the cortisol and cortisone in urine; also by measuring, in one subject, the proportion of 14C and 3H in plasma cortisol and cortisone at intervals after administration. The specific activities were similar, the plasma cortisone was approximately 50 % derived from cortisol at 30 min and the plasma cortisol 40 % derived from cortisone at 40 min. For both the normal subjects given 14C-cortisol and 3H-cortisone the specific activities of the urinary unconjugated metabolites were consistently and markedly higher than those of the hydrolysed conjugated metabolites. The combined secretion rate of 20α- and 20β-dihydrocortisol and tetrahydrocortisol, for one normal subject, was estimated to be approximately 4 mg/24 h. It is suggested that the findings are consistent with the hypotheses that under basal unstressed conditions, 1, cortisol and cortisone are secreted by the adrenal in approximately equal amount; 2, cortisol and cortisone are interconverted at a speed that precludes the liver from being the main site of the interconversion; 3, the major fractions of the unconjugated and conjugated cortisol and cortisone metabolites are formed at different sites.

1972 ◽  
Vol 53 (2) ◽  
pp. 261-276 ◽  
Author(s):  
J. C. MARSHALL ◽  
D. C. ANDERSON ◽  
C. W. BURKE ◽  
A. GALVAO-TELES ◽  
T. RUSSELL FRASER

SUMMARY The effects of clomiphene citrate were studied in nine normal men, in three patients with partial panhypopituitarism, and in four patients with isolated gonadotrophin deficiency. The administration of this drug to the normal subjects in a dosage of 3 mg/kg/day for 10 days resulted in a mean rise in serum luteinizing hormone (LH) of 107%, in plasma 17β-hydroxyandrogens (17-OHA) of 114%, and in plasma total cortisol of 86%. The rise of testosterone concentration in normal subjects was associated with a doubling of the non-protein bound fraction, and also with increased binding of testosterone to sex hormone-binding globulin (SHBG). In contrast, plasma non-protein bound and urinary unconjugated cortisol remained unchanged. The percentage of plasma cortisol not bound to protein fell, indicating that the rise in total plasma cortisol was secondary to increased protein binding. This was confirmed by finding increased binding of both cortisol and testosterone to their specific binding globulins at 1 °C, due apparently to increased concentrations of SHBG and corticosteroid-binding globulin after clomiphene administration. All the responses to clomiphene were prevented by simultaneous administration of fluoxymesterone in two normal subjects. All the hypopituitary patients showed no rise of LH, 17-OHA or cortisol. The hypogonadotrophic patients, however, showed a normal total cortisol rise. It is suggested that clomiphene has two actions. First, it interferes with the hypothalamic feed-back mechanisms for testosterone, resulting in increased LH secretion, and secondly it has an oestrogen-like effect in stimulating production of steroid-binding globulins.


1961 ◽  
Vol 36 (2) ◽  
pp. 237-264 ◽  
Author(s):  
C. Flood ◽  
D. S. Layne ◽  
S. Ramcharan ◽  
E. Rossipal ◽  
J. F. Tait ◽  
...  

ABSTRACT Methods suitable for the estimation of urinary metabolites of aldosterone and of cortisol are described. The excretion of 3H and of 14C in various urinary fractions after the simultaneous injection of 7-3H aldosterone and 4-14C cortisol have been investigated, and the secretion rates of these steroids were estimated. Factors affecting the accuracy of the methods and their suitability for routine use are discussed. Considerable difference was found in the pattern of excretion of 3H and of 14C. In particular, a much larger proportion of the injected tritium was released on extraction at pH. 1. Further, while the total excretion of glucuronide as a percentage of the injected dose was greater for 14C than for 3H, about 72 % of the total tritium in the glucuronide fraction of the first 24 hour urine collection was eluted as a single chromatographic peak, whereas about 60 % of the 14C in the glucuronide fraction was eluted as tetrahydrocortisone, tetrahydrocortisol and allotetrahydrocortisol combined. Excretion values for aldosterone released at pH 1 were obtained for nine normal men after addition of tritiated aldosterone to the urine, and for five normal women and one normal man after injection of the isotope. Excretion values for cortisol metabolites are reported for six normal subjects after injection of 4-14C cortisol. Secretion rates for cortisol were calculated for six normal subjects from the specific activity of the tetrahydro metabolites. The values were 12.2 to 20.5, mean 17.2 mg/d, and agreed with those reported by other workers. The secretion rates for aldosterone, based on the specific activity of the aldosterone released at pH 1 were 50 to 118, mean 77 μg/d.


1960 ◽  
Vol XXXIII (II) ◽  
pp. 168-174 ◽  
Author(s):  
Rona Hurter ◽  
J. D. N. Nabarro

ABSTRACT Aldosterone secretion rates have been measured in six patients with cirrhosis of the liver using 16–3H aldosterone. The proportion of administered radioactivity excreted as pH 1 extractable conjugates and as a glucuronide has also been determined. On unrestricted diets the aldosterone secretion rates were 19, 85 and 94 μg/day in three patients with ascites and oedema, and 140, 170 and 386 μg/day in three without fluid retention. Five of these patients were restudied after at least seven days on a low sodium diet (20 – 30 meq./day) and slight increases of secretion rate observed. The levels obtained were much lower than those previously reported for normal subjects on a low sodium diet. One patient was studied on a subsequent occasion after a haematemesis (urine sodium 1 meq./day), the secretion rate was 1130 μg/day. The proportion of administered radioactivity excreted as glucuronide was below normal in at least one determination on four of the six patients and there was an increase of the proportion excreted as pH 1 extractable conjugates. There was a striking variation of the proportion of radioactivity excreted as pH 1 extractable conjugates. One patient was studied on five occasions and the range was from 6.0 to 25.2 % of the administered radioactivity. This suggests that in patients with cirrhosis of the liver the urinary pH 1 extractable aldosterone may have a variable relationship to the actual secretion rate.


1965 ◽  
Vol 50 (1) ◽  
pp. 131-144 ◽  
Author(s):  
P. Mauvais-Jarvis ◽  
M. F. Jayle ◽  
J. Decourt ◽  
J. Louchart ◽  
J. Truffert

ABSTRACT Normal subjects and hirsute women with micropolycystic ovaries were treated with ethinyl-oestrenol + 3-methoxy-ethinyl-oestradiol (Lyndiol®), in view of studying the action of this compound on the production of androgens and on the urinary excretion of their metabolites. In normal men, the production of testosterone and the excretion of androsterone and aetiocholanolone are suppressed, whereas the excretion of other 17-ketosteroids and the production of dehydroepiandrosterone sulphate are unchanged. Moreover, the luteinizing hormone activity (LH) in plasma is depressed. It seems that the preparation inhibits specifically the testicular androgen production, by suppressing the hypothalamo-hypophyseal control of LH. Testosterone production and urinary 17-ketosteroid excretion are modified in the same way in women with Stein-Leventhal's syndrome. Physiopathological and therapeutical implications which come from these results are discussed.


1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.


1973 ◽  
Vol 72 (4) ◽  
pp. 753-761 ◽  
Author(s):  
Alberto Angeli ◽  
Giuseppe Boccuzzi ◽  
Roberto Frajria ◽  
Daniela Bisbocci ◽  
Franco Ceresa

ABSTRACT 10 mg/kg of dibutyryl cyclic adenosine 3′,5′-monophosphate (Db-cAMP) was iv pulse injected into twelve healthy adult women. The plasma cortisol levels were determined as 11-OHCS at zero time and then at 2.5, 5, 7.5, 10, 15, 30, 60 and 180 min after the injection. The data were compared with those obtained at the corresponding times in two groups of eleven and seventeen healthy women after the injection of 250 ng and 250 μg of synthetic β-1-24 corticotrophin performed in the same manner as the injection of the nucleotide. The mean increments in plasma cortisol were significantly lower after Db-cAMP than after ACTH. Differences were noted by analyzing the time course of the responses. In the case of stimulation with Db-cAMP the 11-OHCS levels rose progressively to a maximum at 15–30 min. By contrast, a peak of plasma cortisol was evident in most cases within a few min after the injection of ACTH; after a fall, a later rise was then observed starting from 15 min. The differences in the plasma 11-OHCS responses after the two stimuli may also be of interest clinically for the investigation of some aspects of adrenal steroidogenesis.


2001 ◽  
Vol 281 (2) ◽  
pp. E349-E356 ◽  
Author(s):  
Mazen J. Hamadeh ◽  
L. John Hoffer

Six normal men consumed a mixed test meal while adapted to high (1.5 g · kg−1· day−1) and low (0.3 g · kg−1· day−1) protein intakes. They completed this protocol twice: when the test meals included 3 mg/kg of [15N]alanine ([15N]Ala) and when they included 30 mg/kg of intrinsically labeled [15N] Spirulina platensis([15N]SPI). Six subjects with insulin-dependent diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test meal with added [15N]Ala while adapted to their customary high-protein diet. Protein restriction increased serum alanine, glycine, glutamine, and methionine concentrations and reduced those of leucine. Whether the previous diet was high or low in protein, there was a similar increase in serum alanine, methionine, and branched-chain amino acid concentrations after the test meal and a similar pattern of15N enrichment in serum amino acids for a given tracer. When [15N]Ala was included in the test meal,15N appeared rapidly in serum alanine and glutamine, to a minor degree in leucine and isoleucine, and not at all in other circulating amino acids. With [15N]SPI, there was a slow appearance of the label in all serum amino acids analyzed. Despite the different serum amino acid labeling, protein restriction reduced the postmeal transfer of dietary15N in [15N]Ala or [15N]SPI into [15N]urea by similar amounts (38 and 43%, respectively, not significant). The response of the subjects with IDDM was similar to that of the normal subjects. Information about adaptive reductions in dietary amino acid catabolism obtained by adding [15N]Ala to a test meal appears to be equivalent to that obtained using an intrinsically labeled protein tracer.


1970 ◽  
Vol 48 (12) ◽  
pp. 1308-1313 ◽  
Author(s):  
A. Shao ◽  
W. Nowaczynski ◽  
O. Kuchel ◽  
J. Genest

A study of the secretion rate of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in normal subjects and patients with benign essential hypertension by a double isotope dilution method showed a fivefold increase in the secretion rate of dehydroepiandrosterone (from 9.8 mg/day ± 3.1 mg/day S.D. to 52.0 mg/day ± 15.5 mg/day S.D.), and a sixfold increase of dehydroepiandrosterone sulfate in hypertensive patients (from 10.7 mg/day ± 2.9 mg/day S.D. to 60.7 mg/day ± 18.6 mg/day S.D.). This study was carried out following the administration of 14C-labelled DHEA and 3H-labelled DHEA-S and involved an initial column chromatographic separation of urinary DHEA-glucuronide and sulfate.


2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Elmy Mariana ◽  
Cece Sumantri ◽  
Dewi Apri Astuti ◽  
Anneke Anggraeni ◽  
Asep Gunawan

The purpose of this research was to determine the effect of heat stress on thermoregulation, haematology, and productivity of Holstein Friesian (HF) dairy cows raised in different elevations. A total of 63 HF in a normal lactation period were used in this study. The research was conducted for 3 months during dry season in three different areas, which were at Pondok Ranggon (97 m.a.s.l) which categorized as a lowland, Ciawi (576 m.a.s.l) which categorized as a lower-upland, and Lembang (1241 m.a.s.l) which categorized as an upland. Observation on microclimate aspects which includes environmental temperature (Ta), relative humidity (RH) and Temperature-Humidity Index (THI) was done by recording each variable for every 2 hours starting from 08.00 to 16.00 WIB. The thermoregulation analysis was done based on the given physiological responses which consisted of the skin temperature (Ts), rectal temperature (Tr), body temperature (Tb), heart rate (Hr), respiratory rate (Rr), Heat Tolerance Coefficient (HTC), plasma cortisol level and haematological profile observation. The Ta, Rr, and THI measurements showed that in the lowland and lower-upland, the HF experienced moderate heat stress, while the HF raised in the upland area experienced less heat stress. The results showed that the dairy cows which raised in lowland had the highest HTC, Tr, Ts and Tb (P<0.05) and lowest Hr (P<0.05). All of the physiological and haematological parameters in the three study area showed a normal value.Furthermore, the erythrocyte, Hb and PVC concentration in a lowland raised HF were higher (P<0.05), while the plasma cortisol levels were not significantly different. The milk production of the observed dairy cows in different elevations was significantly different (P<0.05), with the highest milk yields, were found in the upland raised HF (13.1±3.52 kg), followed by the lower-upland (11.3±4.73 kg) and lowland (7.0±3.36 kg). In general, all of the HF raised in different land elevations was exposed to heat stress during dry seasons, even though the cows showed the ability to physiologically adapt and cope with the conditions. 


1985 ◽  
Vol 108 (2) ◽  
pp. 261-265 ◽  
Author(s):  
V. Coiro ◽  
P. Chiodera ◽  
G. Rossi ◽  
R. Volpi ◽  
M. Salvi ◽  
...  

Abstract. iv administration of oxytocin decreases plasma ACTH-cortisol levels in normal men. In contrast, naloxone, a specific opioid antagonist, stimulates cortisol release, suggesting that opioid peptides exert an inhibitory control on ACTH-cortisol secretion. The present study was carried out in an attempt to determine whether an opioid pathway mediates oxytocin action; therefore, we evaluated the effect of naloxone on the decrease of cortisol induced by oxytocin. Six normal men were treated iv with oxytocin (2 IU as a bolus), naloxone (4 mg as a bolus plus 10 mg infused for 2 h) or a combination of the 2 drugs. Plasma cortisol levels were determined in samples taken before and 2 h after drug treatment. As expected, administration of oxytocin significantly decreased cortisol secretion, while naloxone had a stimulatory effect on plasma cortisol levels. When oxytocin injection was followed by administration of naloxone, cortisol levels remained unchanged; thus, naloxone abolished a cortisol decrement in response to oxytocin. These findings show that in man oxytocin requires an active opioid system in order to produce its inhibitory action on ACTH-cortisol secretion, suggesting that this effect of oxytocin could be mediated by an opioid pathway.


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