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Biomedical subjects

N H Ertel

Publications and source records attributed to N H Ertel.

At least 37 records · Page 2Linked to original sources

Elevated production and metabolic clearance rates of androgens in morbidly obese women.

Blood production rates of testosterone, dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-diol) were found to be approximately 2-fold elevated in morbidly obese, nonhirsute, normally menstruating women. Values were intermediate between those found in normal women and those in a group of nonobese normally menstruating women with idiopathic hirsutism. Elevated androgen production rates in obese women were associated with 2- to 3-fold increases in MCRs, presumably due to decreased levels of sex hormone-binding globulin. Thus, increased production rates were offset by increased MCRs, resulting in plasma testosterone, DHT, and 3 alpha-diol concentrations that were similar in the obese and normal women. By contrast, women with hirsutism had increased production rates associated with elevated plasma androgens as well as increased MCRs. Urinary excretion of testosterone glucuronide and 3 alpha-diol glucuronide (3 alpha-diol G) were elevated in both obese and hirsute women, paralleling the increased androgen production rates. Despite increased production rates and excretion of androgens, obese women exhibited no menstrual abnormalities, hirsutism, or other signs of virilism. To explore the apparent ineffectiveness of increased androgen production to produce virilizing symptoms, we measured plasma 3 alpha-diol G levels as a measure of peripheral androgen action. The mean +/- SE plasma 3 alpha-diol G was 53 +/- 8 ng/dl in obese women and 36 +/- 6 in normal women; by contrast, women with idiopathic hirsutism had levels of 440 +/- 99, a 12-fold elevation. Plasma testosterone glucuronide in obese and hirsute women were only 2- to 3-fold elevated, while plasma DHT glucuronide was not increased in obese women and was only 2-fold elevated in hirsute women. Thus, obesity is a state of increased androgen production and accelerated clearance. 3 alpha-diol G levels in obese women were only minimally elevated, in contrast to values in the hirsute women, perhaps reflecting the apparent androgen ineffectiveness.

Adult↗

Effects of chronic smoking on testosterone metabolism in dogs.

The effects of long-term cigarette smoking on androgen hydroxylases and peripheral hormones were studied in male beagles. In the testis, chronic smoking of high nicotine/tar cigarettes was associated with decreased activity of the 7 alpha-hydroxylase active on testosterone (68% of control, P less than 0.05). Testicular 6 beta and 16 alpha-hydroxylases were not altered. The hepatic androgen 6 beta-hydroxylase activity in control animals was approximately 6 times the testis levels and was stimulated markedly by smoking. This increase ranged from 221% in the low nicotine/tar group (P less than 0.02) to 304% in the high nicotine/tar group (P less than 0.006). Serum testosterone levels were reduced to 54% of control (P less than 0.02) and prostate size to 44% (P less than 0.001) of control with heavy smoking. Serum LH levels were elevated with smoking. These results suggest that chronic cigarette smoking increased hepatic metabolism of testosterone. In addition, serum testosterone levels and prostate size decreased and LH levels increased. Whether the hepatic and the endocrine effects are causally related cannot be determined from this preliminary study.

Animals↗

The metabolic fate of exogenous sorbitol in the rat.

Dietary sorbitol is rapidly converted to fructose and other carbohydrates in the liver, but its metabolic fate has not been studied rigorously. Twenty-four rats were given 20.4 muCi [14C]sorbitol with 100 mg of sorbitol, and groups of six were killed at 1, 3, 6, and 24 hours after sorbitol administration. Rats were also fed 6.9 muCi [14C]sorbitol for 7 or 14 days. Serum, liver, and lens were analyzed for 14C-labeled sorbitol, fructose, and glucose by using high-performance liquid chromatography. Negligible radioactivity (1.1%) was found in the gastrointestinal content at 24 hours indicating virtually complete absorption. Most of the radioactivity was recovered in the glucose fraction in serum, liver and lens. Glucose and fructose concentrations showed some decline by day 14 compared with day 7 in serum and liver. However, in the lens, sorbitol showed a peak value at the end of the 14th day (37.5 +/- 9.9 micrograms/pair). These findings suggest that: 1) after oral administration, sorbitol is completely absorbed, and 2) that there is a finite accumulation of sorbitol and fructose in the lens in 14 days. Although the radioactive label indicated the exogenous origin of these carbohydrates, it is not certain whether the sorbitol is converted to glucose before entering and accumulating in the lens.

Administration, Oral↗

Pheochromocytoma resistant to alpha-adrenergic blockade.

In a 54-year-old man with a norepinephrine-secreting pheochromocytoma, resistance developed to the alpha-adrenergic blocking agent, phenoxybenzamine hydrochloride. Dosages of 240 mg/day were ineffective. Intravenous phentolamine mesylate reduced his BP at first, but resistance developed to this also. Therapy with alpha-methylparatyrosine, an inhibitor of catecholamine biosynthesis, finally controlled his BP, and the tumor was removed.

Adrenal Gland Neoplasms↗

Steroid hormone profiles in women treated with aminoglutethimide for metastatic carcinoma of the breast.

Recent evidence suggests that aminoglutethimide (AG), a known inhibitor of adrenal steroidogenesis, is a potent blocker of aromatase and thus of estrogen production. These properties of AG have been exploited clinically to reduce the biosynthesis of adrenal estrogen precursors and extraglandular estrogen production in postmenopausal women with metastatic breast carcinoma. In this study, we have explored the effects of AG on a variety of steroids, including delta 5-C19 and -C21 compounds and delta 4-C19 and -C21 steroids as well as plasma and urinary estrogens in a series of postmenopausal women with breast cancer treated for 2 to 26 weeks. Plasma concentrations of delta 5-C21 and -C19 compounds were reduced 3- to 5-fold during AG therapy and remained suppressed over the duration of the study. By contrast, the delta 4-steroids such as progesterone, androstenedione, and 17 alpha- hydroxyprogesterone rose 2- to 10-fold during the initial 2 weeks of AG treatment and then fell back to starting levels or were suppressed. Plasma levels of the potent androgens testosterone and dihydrotestosterone were relatively preserved during AG therapy. The possible contribution of the postmenopausal ovary to the above hormone levels during AG therapy was examined by comparing steroid values from surgically castrated and spontaneously menopausal women. No statistically significant differences between the two groups were observed. In response to AG therapy, plasma levels of estrone and estrone sulfate were decreased 61 to 72%, and urinary estrone similarly fell 85% over the 12-week period. Estradiol concentrations in urine and plasma were similarly reduced 40 to 66% from basal values over this same period.

Adrenal Glands↗

Hepatic microsomal induction in rat liver: heterogeneity of response.

The concept that urinary 6-hydroxycortisol excretion patterns reflect all microsomal enzyme activities remains a subject of controversy. Three different microsomal hydroxylase activities were therefore studied in rat liver after the animals were intoxicated with alcohol, phenobarbital, or a combination thereof. The activities of pentobarbital hydroxylase, aniline hydroxylase, and cortisol 6-hydroxylase (the enzyme metabolizing cortisol to 6-hydroxycortisol) were assayed simultaneously after each treatment. A heterogeneity of enzyme activities was noted. Cortisol 6-hydroxylase activity did not parallel the activity patterns of the two other hydroxylases. The data suggest that before urinary 6-hydroxycortisol excretion patterns can be utilized as an index of microsomal enzyme induction, the effect of the specific drug on individual cytochrome P-450 hydroxylases is required.

Aniline Hydroxylase↗

Positive feedback effect of dihydrotestosterone on follicle-stimulating hormone secretion in the male rat: implications and a possible relation to the onset of puberty.

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were measured in serum of adult male rats after 6 days of constant subcutaneous infusion of varying levels of dihydrotestosterone (DHT). Doses from one-half up to the normal "blood production rate" of DHT produced a selective stimulation of serum FSH, but not LH, levels. Higher levels suppressed FSH, LH, and testosterone. Despite the presence of much higher levels of testosterone in blood, the augmentation of FSH secretion indicated in these studies suggests that DHT may have an important role in regulatory systems for gonadotropins.

Animals↗

Elevated prolactin levels in bronchogenic carcinoma.

The frequency and significance of hyperprolactinemia was studied in 21 consecutive, untreated male patients with bronchogenic carcinoma. Seven patients (33%) were found to have elevated serum prolactin (hPRL) levels. No correlation was demonstrated between increased hPRL levels, tissue histology, or tumor burden. L-dopa suppression and/or TRH stimulation tests were obtained in three untreated patients with hyperprolactinemia. The results of these tests were considered normal suggesting hypothalamic control.

Adenocarcinoma↗

Enkephalins and pituitary hormone release: modification of responsiveness to LHRH.

An intraperitoneal injection of leucine-enkephalin into rats stimulates gonadotropin and prolactin release. To elucidate the mechanism of this releasing property of leucine-enkephalin, rat hemipituitaries were incubated with either enkephalin alone or enkephalin in combination with OHRH. Enkephalin alone had no effect on LH or prolactin release in vitro but potentiated the LH response to LHRH. Neither leucine-enkephalin nor LHRH alone had an effect on GH release; however, when combined, a GH response to LHRH occurred. These results suggest that leucine-enkephalin can modify the pituitary responsiveness to certain hypothalamic releasing hormones by a direct pituitary action.

Animals↗

The hypothalamic-pituitary-gonadal axis during hyperthyroidism in the rat.

The rat, an animal without testosterone-estrogen-binding-globulin, was treated with L-T4 to the point of hyperthyroidism in order to study the hypothalamic-pituitary-testicular axis during this condition. Hyperthyroidism led to a significant decline in serum FSH, a fall in serum LH which was not satistically significant, and no change in serum levels of testosterone or estradiol. Testes of hyperthyroid rats produced significantly more testosterone during in vitro incubations than did the testes of control animals. We conclude that hyperthyroidism in the rat leads to a fall in FSH levels either via direct pituitary suppression or via accelerated FSH metabolism. In addition, in vitro studies suggest that excess thyroid hormone may stimulate intratesticular 17 beta-hydroxysteroid dehydrogenase.

Animals↗

Increased estrogen production in obese men.

Serum estrone (E1) and 17beta-estradiol (E2) were noted to be 2-fold elevated in a group of morbidly obese men. Urinary E1 and E2 production rates were elevated in proportion to the degree of obesity, with values as high as 127 and 157 micrograms/day, respectively. Although serum testosterone (T) concentrations were reduced in obese men, averaging 348 +/- 35 vs. 519 +/- 42 ng/dl in lean controls, the dialyzable T fractions were elevated and, hence, the calculated free T concentrations were normal in obese men. Further, the obese men exhibited normal serum LH, FSH, and T responses to clomiphene citrate, indicating intact hypothalamic-pituitary-Leydig cell axes. MCRs of T and peripheral conversion of T to E2 and androstenedione (delta) to E1 were all increased in obese men in proportion to the percentage above ideal weight. Although the obese mean exhibited increased blood levels and production rates of estrogens, there were no signs of feminization, increased T-estrogen-binding, globulin levels, or suppressed basal gonadotropin levels, suggesting a lack of biological effect. We postulate that obese men exhibit defective estrogen receptors, leading to decreased T-estrogen-binding globulin, increased clearance of androgenic hormones, and elevated estrogen production rates.

Body Weight↗

Hyperparathyroidism and coexisting diabetes mellitus. Altered carbohydrate metabolism.

Hyperparathyroidism was diagnosed in a 67-year-old diabetic man treated for 20 years with isophane insulin suspension, 40 to 45 units/day. It was also diagnosed in a 64-year-old diabetic with severe retinopathy and vascular disease, who was not dependent on insulin. In the first case, removal of a parathyroid adenoma resulted in frequent hypoglycemic attacks, which led to a reduction of the administration of insulin isophane suspension to 20 units/day. In the second case, there was a notable improvement in the glucose tolerance testing that followed surgery, accompanied by a decrease in total plasma insulin response from 17,838 to 5,605 units, by planimetry. These observations suggest that hyperparathyroidism worsens coexisting diabetes mellitus and that one must be aware of increased insulin sensitivity and the possibility of severe hypoglycemia in cases that require insulin after surgical correction of the hypercalcemic state.

Aged↗