Presence of fatty acid esters of pregnenolone in follicular fluid from women undergoing follicle stimulation.

In the following investigation the presence of lipoidal pregnenolone derivatives in the preovulatory follicular fluid obtained from women undergoing in vitro fertilization was established. Concentrations of lipoidal pregnenolone proved to be at least twofold greater than those of the unconjugated counterpart. Indirect identification of these lipoidal pregnenolone derivatives was achieved by comparing the C-18 column, thin-layer silica gel (TLC), high performance liquid chromatography (HPLC), and gas chromatography/mass spectrometry (GC/MS) chromatographic properties of the endogenous lipoidal pregnenolone derivatives in follicular fluid with those of synthetic acyl pregnenolone esters.

Formation of lipoidal steroids in follicular fluid.

The presence of high levels of lipoidal pregnenolone in follicular fluid has recently been established although no evidence has been presented concerning its possible origin. The following investigation focuses on the enzymatic conversion of non-conjugated steroids into their lipoidal derivatives in preovulatory follicular fluid obtained from women undergoing in vitro fertilization. Our observations indicated that pregnenolone, an important precursor steroid, was acylated at a similar rate as cholesterol in follicular fluid.

Effect of 3-week treatment with [D-Trp6, des-Gly-NH10(2)]LHRH ethylamide, aminoglutethimide, ketoconazole or flutamide alone or in combination on testicular, serum, adrenal and prostatic steroid levels in the dog.

Adult male mongrel dogs were treated with the LHRH agonist [D-Trp6, des-Gly-NH10(2)]LHRH ethylamide, aminoglutethimide, ketoconazole or flutamide alone or in combination for 21 days before measurement of steroid levels in the testes, prostate, adrenals and serum. Ketoconazole alone caused a marked stimulation of the intra-testicular concentration of pregnenolone, 17OH-pregnenolone, progesterone and 17OH-progesterone with no or little change of androstenedione, testosterone and dihydrotestosterone. Aminoglutethimide caused a 30-95% inhibition in the concentration of all steroids in the tests while treatment with the LHRH agonist caused a near complete inhibition of all testicular steroids.

Local effect of the rabbit embryo-foetus on uterine progesterone and pregnenolone levels.

Rabbit peripheral serum and uterine tissue (embryonic (EZ) and interembryonic (IEZ) zones) were assayed for the main C21, C19 and C18 steroids throughout pregnancy and pseudopregnancy (PSPG). Pregnenolone concentrations in PSPG and IEZ were comparable and remained relatively stable, while its level in EZ increased, reaching a peak value of 18.2 +/- 0.

Extensive esterification of adrenal C19-delta 5-sex steroids to long-chain fatty acids in the ZR-75-1 human breast cancer cell line.

Estrogen-sensitive human breast cancer cells (ZR-75-1) were incubated with the 3H-labeled adrenal C19-delta 5-steroids dehydroepiandrosterone (DHEA) and its fully estrogenic derivative, androst-5-ene-3 beta,17 beta-diol (delta 5-diol) for various time intervals. When fractionated by solvent partition, Sephadex LH-20 column chromatography and silica gel TLC, the labeled cell components were largely present (40-75%) in three highly nonpolar, lipoidal fractions. Mild alkaline hydrolysis of these lipoidal derivatives yielded either free 3H-labeled DHEA or delta 5-diol.

Anti-hormone treatment for prostate cancer relapsing after treatment with flutamide and castration. Addition of aminoglutethimide and low dose hydrocortisone to combination therapy.

The effect of further adrenal androgen blockade with aminoglutethimide (AG) plus low dose hydrocortisone (HC) was studied in 119 patients with clinical stage D2 prostate cancer who previously progressed after standard hormone therapy and were under progression while receiving the combination therapy with Flutamide and castration. Using the objective criteria of the US NPCP, 1 complete, 2 partial and 14 stable responses were obtained for a total response rate of 14.3%, while 102 patients continued to progress.

Influence of diet on plasma steroids and sex hormone-binding globulin levels in adult men.

Several experimental studies have suggested that diet can alter the production and metabolism of steroids in men. The purpose of this study was to determine the levels of unconjugated steroids and steroid glucuronides as well as sex hormone-binding globulin (SHBG) among normal adult men who were either omnivorous or vegetarians. The participants were white volunteers ranging from 25-35 years of age and the blood samples were taken between 0900 h and 1000 h and between 1600 h and 1700 h for two consecutive days.

Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate.

Androgens play a major role in the development, growth, and function of accessory sexual organs, especially the prostate. However, the testis is not the sole source of circulating androgens in man, since the adrenal gland secretes dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (delta 4-dione) in large quantities. The aim of the present study was to investigate the effect of plasma concentrations of DHEA and delta 4-dione similar to those found in adult man on sensitive and specific markers of androgen action in the rat ventral prostate.

Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men.

The concentrations of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione (A-dione), testosterone (T) and dihydrotestosterone (DHT) have been measured before and after castration in men and two animal models, namely the rat and the guinea pig. In adult men, the pre-castration levels of plasma DHEAS and DHEA were measured at 1839 +/- 320 and 2.4 +/- 0.

Androgen metabolites in bovine follicular fluid.

The values of C21-steroids, Delta4-androgens, estrogens as well as 5alpha-reduced steroids have been determined in follicular fluid obtained from superovulated and untreated cows. In the three cows treated with a hormone regimen to induce superovulation, the levels of progesterone and estradiol determined in 3 to 6 follicles per cow ranged from 65 to 448 ng/ml and 1.9 to 8.

Relationship between steroid levels in peripheral serum and uterine tissue during pseudopregnancy in rabbit.

Determination of the main C21, C19 and C18 steroids in peripheral serum and uterine tissue was made to study the relationships of the steroids during pseudopregnancy in the rabbit. Tissue and serum progesterone levels rose significantly (P < 0.01) from estrus to Day 9 and then decreased by 81% (tissue) and 57% (serum) at Day 15, while pregnenolone levels in uterine tissue and serum remained unaffected.

Trends in CHD and risk factors at age 55-64 in the Framingham Study.

In a preliminary analysis to assess secular changes in cardiac morbidity, mortality, and risk factors in the Framingham Heart Study, there is a suggestion of decline in coronary heart disease (CHD) mortality in women but not in men. For subjects age 55 to 64 in 1953, 1963 and 1973, the ten-year CHD mortality rates per 1000 were 93, 84 and 99 for men; and 34, 39, and 24 for women, respectively. In contrast, CHD prevalence rates have increased significantly for men (102, 134 and 159 per 1000) and marginally for women (55, 65 and 69 per 1000).

Contractile properties of human skeletal muscle in childhood and adolescence.

Using a combination of single maximal stimuli and maximum voluntary contractions, a comparison has been made of muscle properties in pre- and post-pubertal male subjects. In the dorsiflexor and plantarflexor muscles of the ankle, the twitch and maximum voluntary torques were approximately twice as large in the older subjects; the mean height and mean weight increased by factors of 1.20 and 1.

Active life among the elderly in the United States: multistate life-table estimates and population projections.

Calculations of multistate life expectancy not only measure how long a population may live beyond a certain age, but also what fractions of this continuing lifetime will be spent in an independent or dependent status. Many Americans aged 70 and over are leading long, active lives; large numbers of individuals who become dependent, moreover, do so temporarily and return to independent status. Men and women have disparate total and active life expectancies, however, reflecting differential survival patterns and varying rates of transition among statuses.

Lipoproteins: carriers of dehydroepiandrosterone fatty acid esters in human serum.

The association between lipoproteins, cholesterol and cholesteryl esters is very well known to facilitate both the transport in plasma and the entry of these non-polar compounds into the cellular compartment. However, recent observations suggest that in addition to cholesterol, lipoproteins contain several other steroids in their lipoidal metabolite forms which may be transported in the very low, low and high density lipoproteins in human serum. Using the important androgen and oestrogen precursor, dehydroepiandrosterone (DHEA), the biosynthetic formation of lipoidal DHEA was demonstrated in human serum.

Determinants of isolated systolic hypertension.

Isolated systolic hypertension (ISH), defined as systolic blood pressure of 160 mm Hg or greater when the diastolic pressure is less than 95 mm Hg, is a common form of hypertension among the elderly. We collected incidence and prevalence data on ISH and evaluated several potential factors for its occurrence in the Framingham Heart Study during 16 biennial examinations. The factors evaluated were age, sex, all components of the blood pressure (systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure), Metropolitan relative weight, serum cholesterol level, serum uric acid level, cigarette smoking, ventricular heart rate, glucose intolerance, and hematocrit.

Effects of the aromatase inhibitor 4-hydroxyandrostenedione and the antiandrogen flutamide on growth and steroid levels in DMBA-induced rat mammary tumors.

Using dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat as model, comparison was made of the effect of treatment for 20 days with the aromatase inhibitor 4-hydroxyandrostenedione (4-OH-A) (7.5 mg, twice daily) or the antiandrogen flutamide (5 mg, twice daily) on tumor growth as well as on plasma and tumor content of estrogens, androgens, and their precursors and metabolites. Tumor number and size were markedly decreased following treatment with either drug, the effect of treatment being more important on size than number, and on new tumors which developed during treatment than on tumors already present at start of treatment.

The rise in testicular androgens during the first days of treatment with an LHRH agonist in the dog can be blocked by aminoglutethimide or ketoconazole.

Up to day 6 of treatment of adult dogs, daily subcutaneous administration of 50 micrograms of the LHRH agonist [D-Trp6, des-Gly-NH2-10]LHRH ethylamide causes up to a 3-fold increase in serum testosterone (T) concentration which is followed by a progressive decrease to castration levels (less than or equal to 0.2 ng/ml) at later time intervals (up to 21 days, the last time interval studied). Both aminoglutethimide and ketoconazole, two inhibitors of steroid biosynthesis, cause a 30-40% rise in serum T when administered alone.

Endocrine effects of combined treatment with an LHRH agonist in association with flutamide in metastatic prostatic carcinoma.

The plasma levels of pituitary hormones (LH, FSH and prolactin) as well as testosterone were determined in 62 patients treated with combined therapy using the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide and the antiandrogen Flutamide. Plasma radioimmunoassayable LH and FSH levels increased to 534% (p less than 0.01) and 150% (p less than 0.

Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate.

In order to assess the androgenic potency of physiological plasma concentrations of the adrenal steroids dehydroepiandrosterone (DHEA) and androstenedione (delta 4-dione) in the rat prostate, these two steroids were released from Silastic tubings of appropriate length and size in castrated male rats. Implants of DHEA led to plasma levels of DHEA and 5-androsten-3 beta,17 beta-diol covering the range of concentrations found in adult men while no significant change was observed in plasma levels of delta 4-dione, testosterone and dihydrotestosterone (DHT). delta 4-Dione implants, on the other hand, led to a parallel increase in plasma delta 4-dione and testosterone levels at all doses used while plasma DHT only increased at supraphysiological doses of delta 4-dione.

Formation of estrogen glucuronides by human granulosa-luteal cells isolated from human menopausal gonadotropin-stimulated cycles for in vitro fertilization.

The formation of steroid glucuronides by human granulosa cells isolated from human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG)-stimulated cycles for in vitro fertilization was studied. From granulosa cells in suspension, 5 x 10(-7) M androstenedione was converted into estradiol (2.50 +/- 0.

Combination therapy with flutamide and [D-Trp6]LHRH ethylamide for stage C prostatic carcinoma.

Sixty-seven previously untreated patients presenting with clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average duration of treatment of 23.5 months. Only five patients have so far shown treatment failure with 91.

A pure antiandrogen does not interfere with the LHRH agonist-induced blockade of testicular androgen secretion in the dog.

Daily subcutaneous administration of 50 micrograms of the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6]LHRH ethylamide in adult dogs causes a transient increase in the serum testosterone (T) concentration which reaches a maximum at 200% above control on days 2-4 of treatment and progressively decreases to 7% of the pretreatment value on day 21, the last time interval studied. After a transient increase, the concentration of serum bioactive luteinizing hormone (LH) was progressively decreased on days 11 and 19, thus suggesting that in analogy with human findings, the loss of LH bioactivity is responsible for the inhibition of testicular steroidogenesis induced in the dog by LHRH agonists. Of major significance is the finding that the changes in serum T levels observed during the first 3 weeks of treatment, as well as the complete inhibition of the intratesticular concentration of sex steroids observed at the end of this period of treatment with the LHRH agonist were not affected by simultaneous administration of flutamide (125 mg per os every 8 h).