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Biomedical subjects

R S Rittmaster

Publications and source records attributed to R S Rittmaster.

64 records · Page 4Linked to original sources
PubMed1987

Hirsutism.

Excess body hair, or hirsutism, is usually only a problem in women and can cause considerable psychological distress. The disorder is usually androgen mediated. Because androgens come only from the adrenal glands or gonads or by conversion in peripheral tissues of precursor steroids from these organs, the causes of hirsutism are found in these two organs. Adrenal causes include Cushing's disease, adrenal tumors, and congenital adrenal hyperplasia. Ovarian causes include tumors, polycystic ovarian syndrome, and most cases of idiopathic hirsutism. The clinical evaluation is designed to differentiate between these diagnostic possibilities. When an underlying abnormality can be identified, such as an ovarian tumor, the treatment course is clear. When the diagnosis is idiopathic hirsutism, however, the best treatment is uncertain and several available regimens are possible.

Androgens↗
PubMed1985

Morphine inhibits the pituitary-adrenal response to ovine corticotropin-releasing hormone in normal subjects.

To determine the locus of opiate modulation of ACTH secretion, 11 normal subjects were given ovine corticotropin-releasing hormone (CRH) 30 min after receiving either placebo or morphine sulfate. Plasma ACTH, cortisol, arginine vasopressin (AVP), epinephrine, norepinephrine, and CRH were measured 30 min before and up to 150 min after CRH administration. Morphine blunted the ACTH response for the first 60 min and cortisol response for the first 90 min after CRH administration. Morphine did not lower arginine vasopressin or catecholamine levels. To determine whether morphine's effect on ACTH and cortisol was due to a direct action on the corticotroph cell, dispersed rat pituitary cells were perifused with medium containing 1 microgram/ml morphine sulfate or medium alone. Morphine had no effect on the ACTH response of these cells to 10 nM CRH pulses. Similarly, morphine had no effect on ACTH production by dispersed rat pituitary cells in monolayer culture in response to 90- and 180-min incubations with 5 nM CRH. We conclude that morphine blunts the early response of the pituitary gland to CRH in vivo. Based on the lack of a direct effect of morphine on rat pituitary cells in vitro, we postulate that morphine given in vivo may modulate the pituitary ACTH response to CRH through other suprapituitary factors.

Adrenocorticotropic Hormone↗
PubMed1985

Growth hormone responses to continuous infusions of growth hormone-releasing hormone.

The pattern of GH secretion during a continuous 4-h iv infusion of 1 microgram/kg.h GH-releasing hormone (1-44)-NH2 (GHRH-44) or saline was examined in 15 adult men. There was prompt release of GH beginning within 20 min of starting the GHRH-44 infusions, reaching peak GH levels of 43 +/- 11 (+/- SE) ng/ml within 60-90 min. This is similar to the peak GH level reached in men after a single 1 microgram/kg GHRH iv bolus dose (34 +/- 8 ng/ml). GH levels then fell progressively, but did not return to baseline during the GHRH infusions. After GHRH infusions, the response (delta) to a 1 microgram/kg GHRH bolus dose was markedly attenuated (delta GH, 2.7 +/- 0.9 ng/ml) compared to the response (delta GH, 23 +/- 3 ng/ml) after saline infusion. Dispersed rat pituicytes perifused with medium containing 10 nM GHRH-44 responded with an initial rapid rise in GH secretion, followed by a progressive decline, and after 150 min of continuous GHRH exposure, the response to pulses of an equal or higher (100 nM) GHRH concentration was blunted. These results indicate that the peak response to GHRH infusions is similar to that of maximally effective bolus doses; during infusions, the GH response is not sustained; and immediately after GHRH infusions, the response to previously effective bolus doses is reduced. These phenomena could reflect either receptor-mediated desensitization, the depletion of rapidly releasable GH stores, or both. A counterregulatory rise in hypothalamic somatostatin secretion is not necessary to produce these effects, since the same phenomenon occurs in vitro and in vivo.

Adult↗
PubMed1985

Sensitivity of cortisol and adrenal androgens to dexamethasone suppression in hirsute women.

To test the hypothesis that adrenal androgen secretion is more easily suppressed than is cortisol secretion by glucocorticoids, we examined the dose-response relationship for suppression of serum dehydroepiandrosterone (DHA), DHA sulfate (DHAS), testosterone, and cortisol by dexamethasone. Nine hirsute women received daily doses of dexamethasone, starting with 0.1 mg and increasing by 0.1-mg increments every 4 weeks, until the cortisol response to ACTH was reduced to 20% or less of the response before treatment. Serum hormone levels were measured at each dexamethasone dose before and after iv administration of 25 U synthetic ACTH. Although low doses of dexamethasone caused a similar suppression of basal cortisol, DHA, and DHAS levels, ACTH-stimulated DHA levels were suppressed to a greater extent than ACTH-stimulated cortisol levels. Higher dexamethasone doses did not result in a significant difference between the degree of cortisol and adrenal androgen suppression, as near-maximal suppression occurred for all three hormones. Maximal suppression of basal testosterone levels occurred at or below the dexamethasone dose of 0.3 mg. We conclude that the adrenal androgen secretory capacity is more sensitive to suppression by dexamethasone than is the adrenal cortisol secretory capacity. Furthermore, glucocorticoid therapy for hirsutism need not achieve complete cortisol suppression to effect a major reduction in adrenal androgen levels.

Adolescent↗
PubMed1984

Potency and specificity of a growth hormone-releasing factor in a primate and in vitro.

The potency and specificity of the 44-amino acid human pancreatic tumor GRF were tested in six adult female rhesus monkeys and in a perifusion system containing a suspension of rat pituicytes. In vivo, plasma GH levels were elevated in a dose-dependent fashion, with an ED50 of approximately 5 micrograms/kg, a value of the same order of magnitude as other hypothalamic releasing hormones. The magnitude of the GH response after GRF treatment was similar to that observed during insulin-induced hypoglycemia, with peak plasma GH concentrations occurring 5-15 min after GRF administration. High doses of GRF slightly stimulated PRL release, but had no effect on arterial blood pressure, heart rate, or plasma cortisol or glucose concentrations. In vitro, GRF released GH in a dose-dependent manner, but no PRL was released even at the highest GRF concentrations employed (100 nM). It thus appears that stimulation of PRL in vivo may be an indirect effect of GRF. Alternatively, there may be species differences in responsiveness to GRF.

Animals↗
PubMedDate not supplied

Effect of MK-906, a specific 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates in normal men.

To determine the hormonal effects of MK-906, an orally active 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates, 12 healthy men were given 10, 20, 50, and 100 mg MK-906 2 weeks apart in randomized order in a 4-period crossover design. Serum testosterone (T), dihydrotestosterone (DHT), androstanediol glucuronide, and androsterone glucuronide were measured before and 24 hours after each dose. The effect of MK-906 on glucuronyl transferase activity, the enzyme responsible for androstanediol glucuronide and androsterone glucuronide formation, was assessed in vitro using rat prostate tissue. Serum T levels were unchanged after all doses. Serum DHT, androstanediol glucuronide, and androsterone glucuronide were suppressed by 70, 40, and 56%, respectively, after the 10-mg dose, and by 82, 52, and 66% after the 100-mg dose (P less than 0.02 for the comparison between the 10 and 100-mg doses for all three steroids), respectively. Baseline serum T and DHT levels were strongly correlated (R = 0.89, P = 0.0002), as were androstanediol glucuronide and androsterone glucuronide levels (R = 0.78, P = 0.003), but there was no correlation between DHT levels and the levels of either conjugated steroid. MK-906 had no effect on glucuronyl transferase activity in vitro. It was concluded that single doses of MK-906 suppress both conjugated and unconjugated 5 alpha-reduced androgens. While all three steroids appeared to be good markers of systemic 5 alpha-reductase inhibition, further research will be needed to determine which steroid best reflects tissue DHT levels in patients receiving these inhibitors.

5-alpha Reductase Inhibitors↗
PubMedDate not supplied

Topical antiandrogens in the treatment of male-pattern baldness.

Antiandrogen therapy for androgen-induced baldness is in its infancy. In men, because of side effects, topical antiandrogens appear to hold the most promise. Assessing changes in scalp hair growth may be difficult, however, and hirsutism provides a useful model for testing the efficacy of topical antiandrogens. Systemic administration of 5 alpha-reductase inhibitors may also eventually prove to be helpful in the treatment of male-pattern baldness, but side effects and long-term risks are unknown. In women, systemic antiandrogens appear to be a reasonable option for therapy and produce a good subjective response. Further research is needed, however, to document the long-term risks and efficacy of systemic antiandrogen therapy in women.

Administration, Topical↗
PubMedDate not supplied

Effect of finasteride on adrenal steroidogenesis in men.

Finasteride, a 5 alpha-reductase inhibitor, does not bind to the androgen receptor and has no other known hormonal activity. To determine what effect, if any, it has on adrenal steroidogenesis, 10 healthy men received 5 mg finasteride daily for 28 days. Adrenocorticotropic hormone (ACTH) stimulation tests were performed before and after 4 weeks of finasteride administration (5 mg daily). Serum levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, deoxycorticosterone, corticosterone, aldosterone, cortisol, dehydroepiandrosterone, and androstenedione were measured before and 60 minutes after i.v. ACTH. Finasteride decreased serum dihydrotestosterone levels from 31 +/- 5 to 4.4 +/- 1.2 ng/dl (P < 0.001). There were no significant changes in basal or ACTH-stimulated serum levels of adrenal steroids. There was also no significant decrease in the product to precursor ratio for the seven adrenal enzymes tested. Finasteride increased mean serum androstenedione levels by 17% (P = 0.10) and significantly increased the androstenedione to 17-hydroxyprogesterone ratio (P = 0.02 before ACTH and 0.05 after ACTH). These changes are most likely due to inhibition of androstenedione metabolism by 5 alpha-reductase. In conclusion, finasteride has no detectable effect on adrenal steroidogenesis, other than that which can be explained by inhibition of the 5 alpha-reductase enzyme.

5-alpha Reductase Inhibitors↗