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Biomedical subjects

D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 325 records · Page 18Linked to original sources
PubMed1978

Adrenarche: a survey of rodents, domestic animals, and primates.

The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man.

Adrenal Glands↗
PubMed1978

Interaction of digitalis and spironolactone with human sex steroid receptors.

Spironolactone and digitoxin have previously been shown to interact with cytosol androgen and estrogen receptors, respectively, in the rat. The interaction of digitoxin with human uterine cytosol estrogen binding protein and spironolactone with human prostate and newborn prepuce cytosol dihydrotestosterone (DHT) binding protein has been analyzed in this study. Specific estradiol binding was found only in premenopausal uteri. The dissociation constant for estradiol binding was 0.6--2.3 X 10(-9) M (n - 12). Digitoxin in concentrations varying between 0.5--2.0 X 10(-6) M inhibited specific estradiol binding with a Ki of 2.0--7.3 X 10(-7) M (n = 9). The dissociation constants for DHT and the human androgen cytosol binding protein in prostate and newborn prepuce were 0.27--3.0 X 10(-8) M (n = 12) and 0.6--2.0 X 10(-8) M (n = 5), respectively. Spironolactone at concentrations of 0.3--2.0 X 10(-6) M competitively inhibited this binding with an affinity about one order of magnitude less than that of DHT. Digitoxin and spironolactone did not displace estradiol and DHT, respectively, from testosterone-estrogen binding globulin in male or female plasma. The interaction of digitoxin with the human uterus estrogen binding protein and spironolactone with the human prostate and prepuce androgen binding protein is similar to our previous observations in the rat, and may explain the weak estrogenic effects of digitoxin and spironolactone in man.

Binding, Competitive↗
PubMed1978

SC 25152: A potent mineralocorticoid antagonist with reduced affinity for the 5 alpha-dihydrotestosterone receptor of human and rat prostate.

It has previously been shown that spironolactone possesses antiandrogenic activity in the rat and interacts with rat prostate 5 alpha-dihydrotestosterone cytoplasmic receptors to block the nuclear uptake of this hormone. Current evidence suggests that this androgen receptor interaction may be an important mechanism through which spironolactone causes endocrine side effects in rat and man. We have analyzed the interactions of several spirolactone analogs with the androgen receptor of human and rat prostate and the mineralocorticoid receptor of human and rat kidney. One analog, SC 25152, was found to have considerably reduced affinity for the prostate 5 alpha-dihydrotestosterone receptor [Ka = 24 +/- 1% and 19 +/- 6% (mean +/- SE) in the human and rat, respectively, of the Ka for spironolactone] while maintaining similar affinity for the mineralocorticoid receptors of human and rat kidney [Ka = 113 +/- 37% and 86 +/- 7% (mean +/- SE), respectively, of the Ka for spironolactone]. These findings would predict this analog to have reduced antiandrogenicity at equivalent therapeutic doses.

Aldosterone↗
PubMed1977

Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss.

We tested hypothalamic, pituitary and endocrine function in 19 patients with secondary amenorrhea associated with simple weight loss who did not have anorexia nervosa to evaluate the effects of weight loss on these systems. Thermoregulation at 10 degrees C and 49 degrees C was abnormal and correlated with the percentage below ideal body weight (r = 0.62, P less than 0.02, and r = 0.55, P less than 0.05, respectively). Partial diabetes insipidus was found in 27 per cent of patients with simple weight loss. They had delayed peak plasma luteinizing hormone levels after 10 microgram of luteinizing-hormone-releasing factor, which was correlated with percentage below ideal body weight (r = 0.49, P less than 0.05). Delayed peak plasma thyrotropin levels after 500 microgram of thyrotropin-releasing factor were found. No prolactin, pituitary, thyroid or adrenal abnormalities were present. These findings are qualitatively similar to results of studies in 29 patients with anorexia nervosa, but less severe and less frequently present. We conclude that hypothalamic dysfunction may be caused by weight loss per se.

Adolescent↗
PubMed1977

Plasma testosterone in homosexual and heterosexual women.

The authors measured plasma testosterone levels in 21 homosexual women and 19 age-matched heterosexual women. Although values for the two groups overlapped considerably, testosterone concentrations averaged 38% higher in homosexual than in heterosexual subjects. A statistically significant inverse correlation between age and testosterone level was found for heterosexual but not for homosexual women.

Adult↗
PubMed1977

Studies on the transfer of steroid hormones across the blood-cerebrospinal fluid barrier in the rhesus monkey. II.

The movement of progesterone (P), cortisol (F) and 17-hydroxyprogesterone (17-OHP) across the blood-cerebrospinal fluid (CSF) barrier was determined using six adult male rhesus monkeys with indwelling canulae in the lateral ventricles of their brains. Tritiated steroids were given iv as a bolus followed by a constant 6 h infusion with continuous collection of CSF and periodic sampling of blood before and during the infusion. The amounts of authentic steroid in the plasma and CSF were determined by recrystallization to constant isotopic ratio and the amount of free plasma steroid was determined by equilibrium dialysis against Ringer's solution. Tritiated progesterone was undetectable in the pooled samples of CSF. The average concentration of tritiated 17-OHP in the CSF was 10.3% of the concurrent plasma level while the concentration of tritiated F was 22.5% of the concurrent plasma level. Plasma free steroid was found to be 2.2% for P, 6.3% for 17-OHP and 22.3% for F, showing a rough correlation between steroid entry into the CSF and free steroid concentration in plasma.

Animals↗
PubMed1977

The effect of osmotic stimuli on prolactin secretion and renal water excretion in normal man and in chronic hyperprolactinemia.

An osmoregulatory role for prolactin (PRL) in man has been postulated, and PRL secretion has been reported to be influenced by osmotic stimuli. Clinical observation, however, does not support this notion. The effects of water loading, hypertonic saline infusion and nicotine on serum PRL and on renal water metabolism were investigated in 6 normal subjects and in 8 patients with chronic hyperprolactinemia (four with and four without demonstrable pituitary tumors). None of the patients had thyroid, adrenal or vasopressin deficiency. Renal walter handling in these patients was indistinguishable from normal. Likewise, serum PRL was not affected by the stimuli employed in either the normal subjects or the patients. No correlation between degree or duration of hyperprolactinemia and renal water metabolism was found. It is concluded that PRL is not an important osmoregulatory hormone in man.

Adult↗
PubMed1976

Androgen binding proteins of testis, epididymis, and plasma in man and monkey.

Androgen-binding protein (ABP) has been found in the cytosol of testicular and epididymal homogenates of several sub-primate species. In those species which had the plasma androgen binding protein, testosterone-estradiol-binding globulin (TeBG), ABP and TeBG were found to be physically similar. We investigated the possibility that ABP might exist in monkey and man using the cytosol of testicular and epididymal homogenates and aspirates obtained by direct micropuncture of the rete testis. In polyacrylamide gel electrophoresis, pH 7.8, testicular and epididymal cytosols of monkey and man were found to contain several binding proteins of different size and net charge that bind dihydrotestosterone. These binding proteins were either indistinguishable from TeBG or could be related to TeBG as size and/or charge isomers. No ABP was detectable in up to 200 mul of monkey rete testis fluid obtained by direct micropuncture, though ABP is detectable in as little as 5 mul of rat rete testis fluid. The data suggest that the ABP's detected in the testicular and epididymal cytosols in monkey and man represent isomeric forms of plasma TeBG, and their presence in testicular cytosol most likely derives from blood contamination.

Androgens↗
PubMed1976

Studies on the transfer of steroid hormones across the blood-cerebrospinal fluid barrier in the Rhesus Monkey.

Indwelling canulae were placed in the lateral ventricles of the brains of six adult male rhesus monkeys, and the movement of estradiol-17beta (E2), testosterone (T), and 5alpha-dihydrotestosterone (DHT) across the blood-cerebrospinal fluid (CSF) barrier was measured. Serial samples of blood and CSF were collected every 30 minutes during a 6 hour infusion of the tritiated steroids, and the quantity of free steroid in the blood and CSF was determined by recrystallization to constant specific activity. During the course of the 6-hour infusion, the average CSF concentration of steroid, expressed as dpm/ml, was about 3.5% of the concurrent plasma level of E2, 1.6% of the concurrent plasma level of T, and 0.08% of the concurrent plasma level of DHT. It is proposed that these differences in steroid transfer can be attributed to differential binding of these steroids to testosterone-estrogen-binding globulin (TeBG) in plasma.

Animals↗
PubMed1976

Mechanism of interaction of digitalis with estradiol binding sites in rat uteri.

Digitalis preparations have a weak estrogenic effect in man. The data in animals are equivocal. We have studied.the biologic effect of both digitoxin and digoxin on the rat uterus in vivo and the interaction of these drugs with the rat uterus estrogen receptor in vitro. Digitoxin and estradiol significantly increased the uterine weight of immature rats, while digoxin did not. The interaction of digitoxin and digoxin with the rat uterus estrogen cytosol receptor was studied using protamine sulfate precipitation and dextran-coated charcoal (DCC) assays. Both methods gave a Kd for the estradiol-receptor interaction between 0.8-3.1 X 10(-9) M (n = 20). Digitoxin at concentrations of 0.5-2.0 X 10(-6) M significantly inhibited the binding of estradiol to the specific or saturable binding sites with minimal inhibition of hormonal binding to nonspecific sites. The binding was competitive with a calculated Ki for digitoxin of 5.2-7.8 X 10(-7) M (n = 18). Digoxin failed to inhibit estradiol binding to the receptor protein in vitro. We conclude that digitoxin probably acts directly as a weak estrogen and that this effect probably explains the estrogen-like side effects seen with digitoxin therapy in man.

Animals↗
PubMed1976

Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.

Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.

Adult↗
PubMed1976

Failure of endogenous prolactin to alter renal salt and water excretion and adrenal function in man.

Prolactin is a salt-retaining hormone in fish, and a similar role is frequently postulated in man, althrough clincial observation does not generally support this. The effect of TRH induced acute elevation of endogenous serum prolactin on renal water, sodium, potassium and total solute excretion was investigated during metabolic balance conditions and during escape form mineralocorticoid excess in 8 normal volunteers (6 males, 2 females)...

Adrenal Glands↗
PubMed1976

An androgen binding protein in the cyst fluid of patients with polycystic ovary syndrome.

Androgen binding proteins (ABP) have not been described in the ovary. We have studied cyst fluids from three patients with the Polycystic Ovary Syndrome and one patient with choriocarcinoma for the presence of ABP. All contained a high affinity, low capacity binding protein for dihydrotestosterone and 17beta-estradiol. Comparison of this protein with the plasma androgen binding protein (TeBG) in polyacrylamide gel electrophoresis and equilibrium dialysis did not reveal any significant differences in molecular size (Kg) net charge (Yo), radius R, molecular weight (mol wt), heat stability, steroid specificity, or binding affinity (Ka). Cyst fluid and plasma could not be distinguished from each other on the basis of protein composition as measured by cellulose acetate electrophoresis. In the one patient studied, the binding capacity for DHT in cyst fluid and plasma was 58.1 and 16.1 ng/Gm protein, respectively.

17-Hydroxycorticosteroids↗
PubMed1976

Delayed pituitary hormone response to LRF and TRF in patients with anorexia nervosa and with secondary amenorrhea associated with simple weight loss.

The qualitative and quantitative responses of LRF-induced LH and FSH release and TRF-induced TSH and Prolactin (PRL) release were evaluated in 21 patients with anorexia nervosa, 19 patients with secondary amenorrhea associated with simple weight loss (SWL) who did not fulfill the psychologic criteria for anorexia nervosa, and 7 normal women in the early follicular phase of the menstrual cycle. Basal plasma LH and FSH were significantly lower in the anorexia nervosa group compared to the SWL group and normals (P less than 0.05). The LRF-induced integrated LH responses, however, were the same in the 3 groups and the integrated FSH responses were greater in the underweight groups when compared to normal. The time of the peak LH response (mean+/-SE) was signifantly delayed (P less than 0.01) in both the anorexia nervosa (49 +/- 6.1 min) and SWL (28 +/- 2.5 min) groups when compared to normal (17 +/- 2.3 min). The time of the FSH response was significantly delayed (P less than 0.05) in anorexia nervosa (95 +/- 9.6 min) when compared to normals (35 +/0 7.9 min) and SWL patients (62 +/- 11.7 min). Normal basal TSH and PRL and normal peak TSH and PRL responses to TRF were found in anorexia nervosa. The time of the TSH and PRL peak (56+/-8.9 and 36+/-3.6 min,, respectively) in anorexia nervosa was significantly later than normal (26 +/- 1.7 and 36 +/- 3.6 min respectively) (P less than 0.01). It is concluded that despite normal quantitative response to releasing hormones, there are abnormally delayed responses in both anorexia nervosa and SWL patients. The SWL responses were intermediate between those of the anorexia nervosa group and normals. The constellation of normal quantitative but abnormal kinetic LRF and TRF responses supports the hypothesis that the endocrine changes seen in anorexia nervosa are consistent with hypothalamic dysfunction.

Adolescent↗
PubMed1976

Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence.

Spironolactone (Aldactone) acts as an antiandrogen by blocking testosterone synthesis and competing with testosterone for the androgen receptor. These properties of the mineralcorticoid antagonist were used in an attempt to interrupt the gonadal-pituitary-hypothalamic negative feedback axis and thereby stimulate LH and FSH in 7 boys with delayed puberty. Following administration of aldactone (5 mg/kg) daily for one week, there was a significant (P less than .01) mean increase in serum LH of 60%. In all 7 boys an absolute rise in LH was observed, but these changes were statistically significant in only 5 individuals. While mean FSH levels increased by 60% in this group of boys, the individual responses were variable. No rise in gonadotropin levels occurred in 2 patients with Kallmann's syndrome, who also received 5 mg/kg of spironolactone daily for 1 week. Large doses of the drug appeared necessary to stimulate gonadotropin secretion since a dose of 3 mg/kg per day did not cause LH or FSH increments in 2 additional patients with delayed puberty. Progesterone and 17alpha-hydeoxyprogesterone levels increased to a greater extent than LH and FSH in response to spironolactone, reflecting either adrenal or testicular enzyme inhibition. Spiornolactone is the first drug shown to be capable of stimulating gonadotropin secretion by interrupting negative feedback inhibition in boys with delayed puberty.

Adolescent↗
PubMed1976

Variable efficacy of glucocorticoids in congenital adrenal hyperplasia.

We have examined the suppression of urinary pregnanetriol and 17-ketosteroids during treatment with cortisol, cortisone, prednisone, and dexamethasone in eight patients with congenital adrenal hyperplasia. A large individual variation in response to each agent was observed. In some individuals, cortisone is less effective than its generally accepted potency would indicate. At equivalent glucocorticoid dosage, dexamethasone was twice as effective as the other steroids in suppressing urinary 17-ketosteroids and pregnanetriol. The potency of dexamethasone in suppressing adrenal function was 80 times that of cortisol, about twice its generally accepted potency as a glucocorticoid or anti-inflammatory agent.

17-Ketosteroids↗