ÉTUDES IN VIVO SUR LE MÉTABOLISME DES ANDROGÉNES APRES ADMINISTRATION DE STÉROÏDES INHIBITEURS DE L'OVULATION

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.

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CLOMIPHENE CITRATE IN MEN: INCREASE OF CORTISOL, LUTEINIZING HORMONE, TESTOSTERONE AND STEROID-BINDING GLOBULINS

Journal of Endocrinology ◽

10.1677/joe.0.0530261 ◽

1972 ◽

Vol 53 (2) ◽

pp. 261-276 ◽

Cited By ~ 41

Author(s):

J. C. MARSHALL ◽

D. C. ANDERSON ◽

C. W. BURKE ◽

A. GALVAO-TELES ◽

T. RUSSELL FRASER

Keyword(s):

Luteinizing Hormone ◽

Plasma Cortisol ◽

Specific Binding ◽

Clomiphene Citrate ◽

Normal Subjects ◽

Sex Hormone Binding Globulin ◽

Total Cortisol ◽

Serum Luteinizing Hormone ◽

Steroid Binding ◽

Normal Men

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.

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Platelet α2-Adrenergic Receptors in Treated and Untreated Essential Hypertension

Clinical Science ◽

10.1042/cs0640265 ◽

1983 ◽

Vol 64 (3) ◽

pp. 265-272 ◽

Cited By ~ 56

Author(s):

Harvey J. Motulsky ◽

Daniel T. O'Connor ◽

Paul A. Insel

Keyword(s):

Essential Hypertension ◽

Urinary Excretion ◽

Adrenergic Receptors ◽

Radioligand Binding ◽

Median Number ◽

Human Platelets ◽

Hypertensive Patients ◽

Receptor Number ◽

Normal Men

1. One hypothesis to account for altered adrenergic response in hypertensive patients is alteration in adrenergic receptors on responsive cells. We therefore used radioligand binding methods to examine the α2-adrenergic receptors on platelets isolated from 17 normal men and from 19 men with essential hypertension. in these studies we used the α2-selective radioligand [3H]yohimbine to determine receptor number and affinity on intact platelets. 2. The median number of receptors per platelet was 265 for the hypertensive patients versus 246 for the platelets of controls. Likewise there was no difference between hypertensives and controls in the dissociation constant of the receptors for [3H]yohimbine or adrenaline. 3. Anti-hypertensive treatment with the α2-agonist guanabenz or the β-antagonist propranolol did not change the number or affinity of platelet α2-receptors. 4. in untreated hypertensives the receptor number did not correlate with age, blood pressure, or 24 h urinary excretion of catecholamines or Na+. 5. We conclude that neither hypertension nor anti-hypertensive treatment alters the number of α2-adrenergic receptors on human platelets. Furthermore, because therapy with an α2-agonist does not alter the receptor number and because the receptor number did not correlate with urinary excretion of catecholamines (an index of sympathetic-nervous-system activity), we conclude that ‘down-regulation’ of human platelet α2-adrenergic receptors may not readily occur in vivo.

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Effect of Picotamide on Platelet Aggregation and on Thromboxane A2 Production In Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648141 ◽

1991 ◽

Vol 65 (03) ◽

pp. 312-316 ◽

Cited By ~ 7

Author(s):

P Minuz ◽

C Lechi ◽

E Arosio ◽

P Guzzo ◽

M Zannoni ◽

...

Keyword(s):

Arachidonic Acid ◽

Single Dose ◽

Platelet Aggregation ◽

Urinary Excretion ◽

Ex Vivo ◽

Thromboxane A2 ◽

Normal Subjects ◽

Dose Aspirin ◽

Induced Aggregation

SummaryEffects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet T×A2 production and on platelet aggregation wpre evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects. Picotamide significantly reduced ADP-induced platelet aggregation, but had no effect on that induced by arachidonic acid or the thromboxane analogue U46619. Though ex vivo platelet T×A2 production (T×B2 concentration after arachidonic-acid-induced aggregation) was reduced from 946 ± 141 (mean ± SD) to 285 ± 91 ng/ml in controls and from 1515 ± 673 to 732 ± 420 ng/ml in patients with arteriopathy, there was no effect on urinary excretion of 2,3-dinor-T×B2 (in vivo indicator of platelet T×A2 production), or on in vivo PGI2 production (urinary excretion of 6-keto-PGF1α and 2,3-dinor-6-keto-PGF1α). In the same subjects, single-dose aspirin reduced ex vivo T×B2 production by at least 98% and 2,3-dinor-T×B2 excretion from 116.7 ± 61.4 to 32.6 ± 17.0 nglg creatinine in control subjects, and from 156.3 ± 66.1 to 59.1 ± 19.2 ng/g creatinine in patients with peripheral arteriopathy. Our data suggest that inhibition of platelet T×A2 production in vivo may not be picotamide’s main mechanism of action.

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ETUDES IN VIVO. SUR LE METABOLISME DES ANDROGENES APRES ADMINISTRATION DE STEROIDES INHIBITEURS DE L'OVULATION

Acta Endocrinologica ◽

10.1530/acta.0.0530037 ◽

1966 ◽

Vol 53 (1) ◽

pp. 37-52 ◽

Cited By ~ 6

Author(s):

Pierre Mauvais-Jarvis

Keyword(s):

Dehydrogenase Activity ◽

Metabolic Pathway ◽

Urinary Metabolites ◽

Hydroxysteroid Dehydrogenase ◽

Before And After ◽

Normal Men ◽

Ethinyl Oestradiol

ABSTRACT Radioactive dehydroepiandrosterone sulfate and testosterone, which are two circulating compounds in humans, have been injected into normal men, women and patients with Stein-Leventhal syndrome. These injections were made before and after administration of ethinyl-oestradiol, lynoestrenol and association of lynoestrenol and mestranol (Lyndiol®). The per cent conversion of injected steroids into 17-ketonic and 17β-hydroxylated urinary metabolites was calculated. The results observed can be summarized as follows: in all cases, the yields of sulfate metabolites formed from radioactive precursors were more important after treatment by antiovulatory steroids, especially urinary dehydroepiandrosterone sulfate derived from injected dehydroepiandrosterone sulfate: aetiocholanolone and androsterone formed from testosterone. The modifications in the 5β/5α ratio of androstanediols suggest that oral synthetic oestrogens and progestins inhibit the 5α-Δ4 reductase implicated in the »17β-hydroxyl metabolic pathway« of testosterone. A change in 17β-hydroxysteroid dehydrogenase activity is also postulated, because testosterone was more metabolized into androsterone via androstenedione, and less reduced into androstanediol after antiovulatory steroids.

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Circadian rhythms of 6-sulphatoxy melatonin, cortisol and electrolyte excretion at the summer and winter solstices in normal men and women

Acta Endocrinologica ◽

10.1530/acta.0.1130450 ◽

1986 ◽

Vol 113 (3) ◽

pp. 450-456 ◽

Cited By ~ 35

Author(s):

D.J. Kennaway ◽

P. Royles

Keyword(s):

Circadian Rhythms ◽

Urinary Excretion ◽

Sodium Excretion ◽

Animal Species ◽

Normal Subjects ◽

Electrolyte Excretion ◽

Urinary Cortisol ◽

Men And Women ◽

Urinary Cortisol Excretion ◽

Normal Men

Abstract. Urinary excretion of 6-suphatoxy melatonin, cortisol, potassium and sodium was monitored at four hourly intervals for 24 h in 30 normal subjects at the summer and winter solstices. The 24 h profiles were fitted to sine curves and mean 24-h excretion, time of maximum excretion and amplitude of the curves compared. The excretion of 6-sulphatoxy melatonin was remarkably stable at the two times of the year (24-h excretion 108 ± 6.3 nmol in summer and 105 ± 6.3 nmol in winter, mean ± sem). The time of maximum excretion was significantly delayed in winter by 1 h and 40 min. Urinary cortisol excretion was significantly higher in winter, however, the amplitude was unaltered. The time of maximum excretion of cortisol was significantly delayed by 1 h and 34 min. Potassium and sodium excretion were both unaffected by seasonal influences. These results contrast with results in some animal species in which the duration of the melatonin signal is thought to be the key determinant in subsequent melatonin action. In humans it is likely that the phasing of the melatonin rhythm is of prime importance.

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Urinary Excretion of Erythropoietin in Normal Men and Women

Blood ◽

10.1182/blood.v28.3.344.344 ◽

1966 ◽

Vol 28 (3) ◽

pp. 344-353 ◽

Cited By ~ 54

Author(s):

RAYMOND ALEXANIAN ◽

Brenda Prewitt

Keyword(s):

Urinary Excretion ◽

Dose Response ◽

Normal Subjects ◽

Adult Males ◽

Response Relationship ◽

Dose Response Relationship ◽

Men And Women ◽

Linear Dose ◽

Prepubertal Boys ◽

Normal Men

Abstract The bioassay of erythropoietin in polycythemic mice was modified to include a protein-depletion diet and a divided erythropoietin injection schedule. Although less than 0.05 unit of standard erythropoietin was not detected, a more linear dose/response relationship resulted from increasing doses of erythropoietin in the 0.1 to 1.0 unit range. The amount of erythropoietin in concentrated specimens prepared from the 24-hour urinary excretion of 25 normal subjects was measured in comparison with known quantities of standard erythropoietin. A mean daily erythropoietin excretion in men of 2.8 ± 1.3 units, in women of 0.9 ± 0.4 unit and in prepubertal boys of 1.0 unit was calculated. The higher erythropoietin excretion in adult males may be secondary to a greater production of erythropoietin in this sex.

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Temporal coupling among luteinizing hormone, follicle stimulating hormone, β-endorphin and cortisol pulse episodes in vivo

Acta Endocrinologica ◽

10.1530/acta.0.1260193 ◽

1992 ◽

Vol 126 (3) ◽

pp. 193-200 ◽

Cited By ~ 12

Author(s):

Johannes D Veldhuis ◽

Michael L Johnson ◽

Eugene Seneta ◽

Ali Iranmanesh

Keyword(s):

Luteinizing Hormone ◽

Follicle Stimulating Hormone ◽

Hormone Release ◽

Likelihood Functions ◽

Statistical Confidence ◽

Temporal Coupling ◽

Pulsatility Pattern ◽

Normal Men ◽

Stimulating Hormone

We have applied explicit probability equations to assess possible non-random associations among four distinct hormone series consisting of episodic luteinizing hormone, follicle stimulating hormone, β-endorphin, and/or cortisol pulses observed under physiological conditions in normal men. Closed-form likelihood functions permitted us to demonstrate significantly coordinated patterns of multiple hormone release. A specific quadruple co-pulsatility pattern was observed, in which the two gonadotropic hormones (luteinizing hormone and follicle stimulating hormone) were co-secreted and coupled by a 10-20 min lag to the later release of β-endorphin. In turn, β-endorphin release episodes were followed within 0–30 min by cortisol bursts. Conditional probability analysis allowed us to reject with high statistical confidence the null hypothesis that this unique temporally specified pattern of quadruple hormone release was due to purely random associations among the four pulsatile series. We conclude that discrete hormone release episodes associated with four hormones within the gonadotropic and corticotropic axes in man exhibit significantly lagged non-random temporal coupling in vivo.

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Calcium antagonists and hormone release

Acta Endocrinologica ◽

10.1530/acta.0.1010005 ◽

1982 ◽

Vol 101 (1) ◽

pp. 5-9 ◽

Cited By ~ 6

Author(s):

Antonino Barbarino ◽

Laura De Marinis ◽

Antonio Mancini ◽

Ofa Makhoul

Keyword(s):

Luteinizing Hormone ◽

Calcium Antagonists ◽

Essential Role ◽

Normal Subjects ◽

Constant Infusion ◽

Second Phase ◽

Lh Release ◽

Two Phases

Abstract. Recent in vitro studies have demonstrated that Ca2+ plays an essential role in gonadotrophin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. In vivo, we have previously shown that verapamil, a substance known to inhibit calcium entry into cells, is capable of inhibiting basal gonadotrophin release as well as the release of luteinizing hormone and follicle-stimulating hormone (FSH) in response to an iv bolus of GnRH. We have examined the effects of calcium antagonists on the two phases of pituitary LH release in response to constant GnRH infusion in normal subjects. In 6 men, constant infusion of GnRH (0.2 μg/min × 4 h) resulted in the expected biphasic LH response, with an initial rapid release of LH during the first hour of infusion, followed by a second phase release during the subsequent 3 h. When verapamil (5 mg/h) was infused together with GnRH over a 4 h period, a significant decline of the rapid as well as delayed release of pituitary LH occurred. During the calcium antagonist infusion FSH release was also inhibited, indicating that Ca2+ is also important for the release of this hormone. Our data demonstrate that Ca2+ plays an essential role in the mechanism of GnRH action on both phases of LH release and the release of FSH in normal subjects.

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