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Biomedical subjects

D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 307 records · Page 17Linked to original sources
PubMed1979

Neuroendocrine effects of haloperidol in an adolescent with Gilles de la Tourette's disease and delayed onset of puberty.

The effects of haloperidol on the release of prolactin, growth hormone, and luteinizing hormone during sleep were studied in an adolescent male who had Gilles de la Tourette's disease and delayed onset of puberty. At doses of 5 and 2 mg, haloperidol led to an increase of prolactin secretion and a suppression of luteinizing hormone release. Growth hormone was unaffected. Despite these changes, the patient had normal secondary sexual development consistent with puberty.

Adolescent↗
PubMed1979

Evidence that testosterone can suppress pituitary gonadotropin secretion independently of peripheral aromatization.

Testosterone (T) was given to normal men with and without the concomitant administration of the aromatase inhibitor, delta 1-testolactone (Teslac), to examine the role of peripheral aromatization of T in gonadotropin regulation. When T was administered alone by continuous iv infusion (15 mg/day for 4 days), serum T increased 3-fold (P less than 0.01) and estradiol (E) increased by 50% (P less than 0.01). These changes were associated with a 50% decrease in serum LH and FSH concentrations (P less than 0.01). When T was infused into men taking Teslac (2000 mg/day), serum T levels doubled (P less than 0.01), but E levels did not change (13.4 +/- 1.5 vs. 13.5 +/- 1.0 pg/ml; P = NS). This pattern of plasma steroids, increased T and unchanged E, was also associated with significantly decreased serum LH and FSH concentrations (14.5 +/- 0.4 vs. 8.0 + 0.4 mIU/ml and 9.9 +/- 2.5 vs. 5.8 +/- 0.1 mIU/ml, respectively; P less than 0.01). These data support the hypothesis that T or one of its metabolites can modulate LH and FSH secretion independently of peripheral aromatization to E.

Adult↗
PubMed1979

Dissociation of cortisol and adrenal androgen secretion in patients with secondary adrenal insufficiency.

Plasma cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (delta4-A) were measured by RIA during ACTH infusion in preadrenarchal children with constitutional short stature, normal adults, and patients with secondary adrenal insufficiency resulting from hypothalamic-pituitary disease or corticosteroid therapy. The plasma levels of all four steroids were decreased in patients with secondary adrenal insufficiency compared to normal adults, but the decrease in DHA and DHAS was considerably greater than that in cortisol and delta4-A, resulting in significant decreases in the plasma ratios of DHA to cortisol, DHAS to cortisol, DHA to delta4-A, and DHAS to delta4-A (P less than 0.00001). The decreased DHA and DHAS responses to ACTH persisted in one glucocorticoid-treated patient after glucocorticoid therapy was terminated and the cortisol response to ACTH had normalized. The data suggest that adrenal atrophy due to hypothalamic-pituitary disease or corticosteroid therapy is associated with a greater impairment in the secretion of the delta5 adrenal androgens DHA and DHAS than in the secretion of cortisol and delta4-A, and that the capacity to secrete cortisol and delta4-A recovers more rapidly than the capacity to secrete the delta5 adrenal androgens when corticosteroid therapy is withdrawn.

Adolescent↗
PubMed1979

Relative binding of testosterone and estradiol to testosterone-estradiol-binding globulin.

The binding of estradiol (E2) and testosterone (T) to testosterone-estradiol-binding globulin (TeBG) was studied in vivo at 37 C by three independent methods: equilibrium dialysis, steady state polyacrylamide gel electrophoresis, and TeBG-ligand dissociation kinetics. Equilibrium dialysis was performed at 37 C with the dialysate containing human serum albumin in amounts equivalent to that of the plasma dialysand. Scatchard analysis indicated that under these conditions E2 does not measurably bind to TeBG, while T has a Kd of 3.7 X 10(-10) M. Similarly, Scatchard-type analysis of E2 binding to TeBG in steady state polyacryalmide gel electrophoresis at 37 C revealed no high affinity saturable binding, while dihydrotestosterone was bound with a Kd of 2.7 X 10(-10) M. Examination of the dissociation kinetics of T and E2 ffrom TeBG revealed that the mean (+/-SD) T1/2 of dissociation of T from plasma at 37 C (10.8 +/- 2.4 min) was significantly shortened to 3.5 +/- 0.4 min by saturation of plasma with dihydrotestosterone (P less than 0.01), whereas that of E2 (8.9 +/- 1.4 min) was not changed (9.6 +/- 3.0 min). These data suggest that TeBG is not an important binder of plasma E2 at physiological temperatures and explain the observation that in diseases characterized by high TeBG levels, such as hyperthyroidism and liver disease, the MCR and free E2 levels have generally been normal.

Adult↗
PubMed1979

Replacement oral ethinyloestradiol therapy for gonadal dysgenesis: growth and adrenal androgen studies.

We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with low-dose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and public hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 +/- 0.9 cm/year pre-treatment to 5.3 +/- 1.5 cm/year (P less than 0.02) in the first year. There was deceleration to 1.9 +/- 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased public hair and growth in these patients.

Administration, Oral↗
PubMed1979

Cimetidine is an antiandrogen in the rat.

Cimetidine has been associated with gynecomastia as a side effect. Because other antiandrogens have been linked to the development of breast enlargement in men, the suggestion by earlier workers that cimetidine possessed antiandrogenic properties prompted us to study the endocrine effects of cimetidine in rats. Cimetidine directly antagonized the effects of exogenously administered testosterone on androgen target tissues. Ventral prostate and seminal vesicle weights were less in cimetidine-treated castrate adult male rats androgenized with testosterone-filled subcutaneous silastic capsules than in vehicle-injected controls. Cimetidine possessed no intrinsic androgen-like bioactivity in prepubertal male rats when given in doses of 50 mg/kg/day for 1 wk. Cimetidine competitively inhibited DHT binding to its cytoplasmic receptor and decreased specific nuclear uptake of [3H]dihydrotestosterone in rat ventral prostate slices. No effects on plasma gonadotropin or testosterone concentrations were observed. We conclude that cimetidine is a nonsteroidal-antiandrogen and that this property may contribute to the production of gynecomastia in cimetidine-treated men.

Androgen Antagonists↗
PubMed1979

SC 25152: a potent mineralocorticoid antagonist with decreased antiandrogenic activity relative to spironolactone.

The widely used mineralocorticoid antagonist spironolactone has antiandrogenic activity that may contribute to its side effects of decreased libido, impotence and gynecomastia. We have therefore sought a less antiandrogenic analog of spironolactone that may exhibit reduced endocrine side effects. The analog SC 25152 was chosen for pharmacological testing because of the previous observation that it has considerably reduced affinity for the androgen receptor of both man and rat but exhibits an affinity for the mineralocorticoid receptor similar to that of spironolactone. Bioassays in the rat show that SC 25152 has a 60% decrease in antiandrogenicity, and a 4-fold increase in antimineralocorticoid activity compared to spironolactone, resulting in an overall reduction of antiandrogenic activity to one-tenth that of spironolactone at doses giving equal antimineralocorticoid activity. These studies demonstrate that the antiandrogenic and antimineralocorticoid activities of spironolactone analogs can be dissociated and illustrates the utility of measurements of drug-receptor interaction to identify a compound with desired pharmacological properties.

Adrenalectomy↗
PubMed1978

Failure of breast cancer cells in long-term culture to aromatize androstenedione.

The ability of breast cancer cells in long-term tissue culture to aromatize androstenedione to estrone and estradiol was examined. (3H) androstenedione (1.1 x 10(-7)M) was incubated with 9 cell lines of human breast cancer and one line derived from a dimethylbenz(a)anthracene induced rat mammary tumor. No conversion to estrone or estradiol was detected. The findings are discussed in light of previous studies showing aromatization of androgens in breast cancer tissues.

Androstenedione↗
PubMed1978

The effect of the administration of spironolactone on the concentration of plasma testosterone, estradiol and cortisol in male dogs (1).

The effect of the administration of spironolactone, deacetylspironolactone, aldadiene or soldactone on the concentration of plasma testosterone, estradiol, and cortisol was examined in male dogs. Decreases of 60 to 75% in plasma testosterone and estrodiol occur only at high doses (100 mg/kg) of spironolactone or deacetylspironolactone but not at low doses of spironolactone (5 to 10 mg/kg); they occur concomitantly with similar decreases of androgen formation by the testis. No decreases were detected with aldadiene or soldactone. Treatment of dogs with spironolactone (100 mg/kg) also lowered by 50 to 65% the concentration of cortisol in adrenal venous plasma.

Animals↗
PubMed1978

Suppression of plasma luteinizing hormone by prolactin in the male rat.

Although a direct effect of PRL on gonadotropins has been previously suggested, it has not been convincingly demonstrated. The secretion of LH and FSH was studied in response to the stimuli of castration and LH releasing hormone administration in adult male rats made hyperprolactinemic with ectopic pituitary glands. Although plasma LH and FSH levels were similar in non-castrate hyperprolactinemic rats vs. controls, LH concentrations 24 h postcastration were less in hyperprolactinemic animals as compared to controls (P less than 0.001). The level of LH achieved was inversely correlated with the PRL concentration generated (r = -0.71; P less than 0.01). LH suppression was evident in hyperprolactinemic rats at 1 and 3 days postcastration but was no longer observable at 7 days postcastration. After LH releasing hormone administration to non-castrate rats the rise in plasma LH was significantly less in the hyperprolactinemic animals (P less than 0.05). These experiments support the hypothesis that PRL directly inhibits LH secretion, presumably at the pituitary level.

Animals↗
PubMed1978

Rat adrenal androgen receptor: a possible mediator of androgen-induced decreased in rat adrenal weight.

Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems.

Adrenal Glands↗