J Nutr. 1984 Jul;114(7):1242-51.
Effect of dehydroepiandrosterone on growth in lean and obese Zucker rats.

Cleary MP, Shepherd A, Jenks B.

Several studies were undertaken to determine the effect of dehydroepiandrosterone (DHEA) on growth in Zucker rats. In experiment 1, 3 weeks of DHEA treatment in lean rats resulted in decreased body weight gain in comparison to control rats. In experiment 2, both lean and obese rats were treated with DHEA from 6 to 21 weeks of age. Significant decreases in body weight were found for both lean and obese DHEA-treated rats. The food efficiency ratio (FER) was significantly decreased in both DHEA-treated groups. Significant decreases in parametrial and retroperitoneal fat pads were found in both lean and obese DHEA-treated rats. This was primarily attributed to a decrease in fat cell number in lean rats and to decreases in both number and size of fat cells in obese rats. In experiment 3 obese female rats were treated with DHEA from 6 to 21 weeks of age followed by 15 weeks with DHEA removed from the diet. Significantly more weight was gained by the rats previously treated than by the control rats, but body weight remained significantly lower than in the control groups. These data indicate DHEA has an effect on altering body weight and body fat in lean and obese Zucker rats.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6234382&dopt=Abstract DHEA




J Clin Endocrinol Metab. 1984 Sep;59(3):471-7.
Testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in hyperandrogenic women.

Steinberger E, Smith KD, Rodriguez-Rigau LJ.

Serum levels of testosterone (T), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) were measured in a group of 285 women with clinical signs of hyperandrogenism (hirsutism and/or acne). Levels of T were elevated in 75.8% of the patients, DHEA in 57.5%, and DHEA-S in 20%. Normal levels of all 3 androgens were found in 13.3%. Significant correlations were demonstrated among levels of all androgens. Only 7.7% of the patients had elevated levels of DHEA in the presence of normal T, and 3.2% had elevated DHEA-S and normal T levels. Subdivision of the study population on the basis of presence of acne, hirsutism, or both demonstrated no significant differences in androgen levels. Amenorrheic women had higher serum T levels than those with menstrual cycles. Women with laparoscopically demonstrated polycystic ovaries had significantly higher serum androgen levels than hyperandrogenic women with no laparoscopic evidence for polycystic ovarian disease. All 285 patients were treated with chronic low dose prednisone therapy. Overall suppression of all 3 androgens occurred in a large proportion of the patients. The pretreatment levels of DHEA or DHEA-S did not predict the responsiveness of T to chronic glucocorticoid therapy. On the other hand, a 2-day dexamethasone (DEX) suppression test quantitatively predicted the degree of T suppression achieved by chronic therapy. An overnight DEX suppression test was considerably less precise for this purpose. In conclusion, chronic low dose prednisone therapy resulted in suppression of serum T levels in a large proportion of women with hyperandrogenism of undetermined cause. The response to therapy could not be predicted on the basis of pretreatment serum DHEA or DHEA-S levels, but was predicted with a 2-day DEX suppression test.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6235239&dopt=Abstract DHEA [PubMed - indexed for MEDLINE]




Clin Invest Med. 1984;7(2):119-22.
Dehydroepiandrosterone sulfate: kinetics of metabolism in normal young men and women.

Bird CE, Masters V, Clark AF.

The constant infusion technique was used to study the kinetics of dehydroepiandrosterone sulfate (DHEAS) metabolism in normal young men and women. The metabolic clearance rates (MCR) (means +/- SEM) for normal young men and women were 15.2 +/- 1.7 1/24 h (8.2 +/- 0.7 1/m2/24 h) and 11.8 +/- 0.8 1/24 h (7.3 +/- 0.4 1/m2/24 h) respectively. Coupled with the plasma levels of 5.07 +/- 1.95 and 4.02 +/- 0.57 mumole/L the resulting blood production rates were 76.7 +/- 25.7 and 48.0 +/- 9.4 mumole/24 h for men and women respectively. The conversion ratios for the conversion of DHEAS to dehydroepiandrosterone (DHEA) were 0.006 for men and 0.004 for women. Because of the high metabolic clearance rates for DHEA relative to those for DHEAS and the high production rates of DHEAS most of the DHEA produced per day can arise from DHEAS.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6236000&dopt=Abstract DHEA




Fertil Steril. 1984 Jul;42(1):76-81.
The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women.

Hoffman DI, Klove K, Lobo RA.

One hundred nineteen euprolactinemic anovulatory infertility patients who were being evaluated for induction of ovulation with clomiphene citrate were studied to determine the prevalence of increased adrenal androgen (AA) secretion in this group. Fifty percent of these patients exhibited increased AA secretion, as evidenced by an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level. Seventy-seven percent of these women with elevated levels of DHEA-S were nonhirsute . Twenty-six patients with elevated serum DHEA-S levels underwent adrenocorticotropic hormone (ACTH) stimulation tests in order to determine a possible mechanism(s) for the increase in DHEA-S. Plasma ACTH, as well as total, low-density lipoprotein, and high-density lipoprotein cholesterol were also measured. These levels were normal and did not correlate with the elevated levels of DHEA-S. Seven of 16 patients (34%) had exaggerated responses of serum DHEA-S and of 17-OH pregnenolone to ACTH stimulation. In six of these seven patients, our data suggested the occurrence of a mild deficiency of 3 beta-ol dehydrogenase-isomerase. All of these six patients were considered to have polycystic ovary syndrome. While these data do not explain the increased AA secretion in the majority of patients with elevated levels of DHEA-S, we suggest that serum DHEA-S is frequently elevated in anovulatory infertile patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6327404&dopt=Abstract DHEA




J Nutr. 1986 Feb;116(2):304-10.
The effect of dehydroepiandrosterone on liver metabolites.

Casazza JP, Schaffer WT, Veech RL.

Liver metabolites and in vitro enzyme activities were measured in Sprague-Dawley rats pair-fed the standard NIH diet with or without 0.6% (wt/wt) dehydroepiandrosterone (DHEA) for 16 d. Absorption of DHEA from the gut was confirmed by a 300-fold increase in urine 17-ketosteroids in DHEA-treated animals. Of the liver metabolites measured only 6-phosphogluconate was significantly changed, increasing by less than a factor of two in the DHEA-treated animals, 38.7 +/- 2.2 nmol/g, above the value in the pair-fed controls, 22.5 +/- 2.5 nmol/g. Contrary to the in vitro findings that DHEA inhibits glucose-6-phosphate dehydrogenase (EC 1.1.1.49), thus leading to the hypothesis that DHEA inhibits fat synthesis by diminishing the availability of NADPH, the [NADP+]/[NADPH] ratios calculated from the 6-phosphogluconate dehydrogenase (EC 1.1.1.44), isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40) redox couples were no more oxidized in the DHEA-treated animals than in the control animals. Malic enzyme and isocitrate dehydrogenase activities were 620 and 25% higher in DHEA-treated animals than in pair-fed controls. There was no change in the measured activity of glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase. These data give no support to the hypothesis that administration of DHEA per os results in decreased cytoplasmic NADPH in liver.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2935600&dopt=Abstract DHEA




Endocrinol Jpn. 1985 Oct;32(5):691-700.
Mechanism of dissociation of cortisol and adrenal androgen secretion after removal of adrenocortical adenoma in patients with Cushing's syndrome.

Nawata H, Higuchi K, Yanase T, Takayanagi R, Kato K, Ibayashi H.

We investigated the mechanism of dissociation of cortisol and dehydroepiandrosterone sulfate (DHEA-S) secretion by the adrenal glands after the removal of an adrenal gland containing an adrenocortical adenoma in a patient with Cushing's syndrome. After removal of the adrenocortical adenoma, the serum cortisol rapidly decreased from 24.6 +/- 6.4 micrograms/dl (mean +/- SD, n = 6) to 0.7 +/- 0.5 micrograms/dl. Serum DHEA-S levels were 15 +/- 14 micrograms/dl and 6 +/- 9 micrograms/dl before and after surgery, respectively, and significantly lower than the control values. Serum cortisol levels reverted to normal levels 1.5 to 3 years after the surgery. On the other hand, DHEA-S levels reverted to normal 5 to 7 years after the serum cortisol levels had normalized. Monolayer cultures of normal human adrenal cells obtained at adrenalectomy in patients with advanced breast cancer and atrophic adrenal cells adjacent to the adrenocortical adenoma in patients with Cushing's syndrome were used to study the mechanism of the dissociation of cortisol and DHEA-S secretion. ACTH caused significant increases in the productions of pregnenolone (P5), progesterone (P4), 17-hydroxypregnenolone (17-OH-P5), 17-hydroxyprogesterone (17-OH-P4), DHEA, DHEA-S, androstenedione (delta 4-A), and cortisol. The amounts of 17-OH-P5 and 17-OH-P4 produced by ACTH in atrophic adrenal cells were significantly greater than those in normal adrenal cells. The amounts of DHEA, DHEA-S and delta 4-A produced by ACTH in atrophic adrenal cells were significantly smaller than those of normal adrenal cells. The conversion rate of 17-OH-[3H]P5 to 17-OH-[3H]P4 and 11-deoxy-[3H] cortisol was higher in atrophic adrenal cells than in normal adrenal cells, but the conversion rate to [3H]DHEA, [3H]DHEA-S




J Clin Endocrinol Metab. 1986 May;62(5):812-5.
Levels of plasma steroid glucuronides in intact and castrated men with prostatic cancer.

Belanger A, Brochu M, Cliche J.

The levels of plasma dehydroepiandrosterone (DHEA), androst-5-ene-3 beta,17 beta-diol (delta 5-diol), testosterone (T), dihydrostestosterone (DHT), androstane-3 alpha,17 beta-diol (3 alpha-diol), androsterone (ADT), and the related glucuronide (G) derivatives were determined in intact and castrated men with prostatic cancer. The plasma concentrations of DHEA and DHEA-G were not significantly different in intact and castrated men while delta 5-diol as well as delta 5-diol-G were 50% lowered in castrated men. As expected, T and DHT concentrations were markedly lower in castrated men. These low plasma levels of T and DHT were accompanied by a decrease of 3 alpha-diol, ADT, T-G, 3 alpha-diol-G, and ADT-G levels. There was, in unoperated men, a positive correlation between the levels of DHEA and ADT-G as well as DHEA and DHEA-G, while T values were highly correlated with ADT-G and 3 alpha-diol-G levels. Furthermore, a significant relationship was found between DHEA and ADT-G as well as 3 alpha-diol-G in castrated men. Our data clearly demonstrate that ADT-G and 3 alpha-diol-G levels are more affected by castration than are the corresponding unconjugated steroids and suggest that these steroid glucuronides should be good markers of androgen metabolism. Moreover, the significant relationship between DHEA, ADT-G, and 3 alpha-diol-G in castrated men also suggests that approximately 30% of C-19 steroids from the adrenals are converted to T and DHT, which are further transformed into steroid glucuronides.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2937801&dopt=Abstract DHEA




J Clin Endocrinol Metab. 1986 Jun;62(6):1322-4.
Failure of dehydroepiandrosterone enanthate to promote growth.

Sizonenko PC, Paunier L.

Adrenal androgens may promote pubertal growth. To assess this possibility, we administered dehydroepiandrosterone (DHEA) enanthate in monthly im injections in a dose of 70 mg/m2 for 1 yr to five boys with constitutional short stature (aged 11-13 4/12 yr) and one boy (aged 13 4/12 yr) with panhypopituitarism (coincidentally receiving T4 and human GH). All had bone age delay of at least 3 yr and subnormal levels of DHEA and DHEA sulfate (DHEA-S) for their chronological age. Pretreatment growth velocity ranged from 3-5 cm/yr. After DHEA enanthate injection, plasma DHEA levels were increased 10-fold after 8 days, 2.6-fold after 15 days, and 1.8-fold after 22 days. At the same times, plasma DHEA-S concentrations were 14-, 6-, and 4-fold increased, respectively. There was no rise in plasma testosterone and delta 4-androstenedione, which remained at prepubertal levels. During the year of therapy and for 1 yr after therapy, there was no significant change in growth velocity, and the rate of skeletal maturation assessed by x-ray was not affected. Three of the five boys with constitutional short stature entered puberty within 1 yr after discontinuation of therapy. These results demonstrate that this long-acting form of DHEA administered for 1 yr did not raise plasma testosterone above prepubertal levels and did not accelerate either growth or skeletal maturation. These findings do not support the possibility that DHEA plays a role in normal growth.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2939100&dopt=Abstract DHEA




Fertil Steril. 1983 Apr;39(4):499-504.
Peripheral androgen levels in danazol-treated premenopausal women.

Carlstrom K, Doberl A, Rannevik G.

Eighteen normally menstruating women with endometriosis were treated with 600 mg of danazol daily for 6 months. Blood samples were taken before and after 2, 4, 8, 12, and 16 weeks of treatment and were analyzed for plasma dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and testosterone (T) and for serum alanine aminotransferase (ALAT), albumin, creatinine, potassium, and sodium. The basal values of all parameters studied were well within normal reference limits. DHEA-S was significantly increased at 2, 4, and 8 weeks, and DHEA significantly decreased at 8 and 12 weeks of treatment. The ratio between DHEA and DHEA-S was significantly decreased at weeks 4, 8, 12, and 16. T was significantly decreased during the whole period of observation. ALAT was significantly increased at weeks 4, 8, 12, and 16. A slight but significant increase was observed for creatinine and potassium, while no changes were observed for albumin and sodium. Of the two major androgen sources, the adrenal cortex appears to be relatively unaffected; whereas the ovary may be affected to a minor degree. Therefore, it seems likely that the changes observed in DHEA and DHEA-S may be due to minor alterations in renal and hepatic turnover rather than an effect on adrenal steroidogenesis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6219898&dopt=Abstract DHEA




Maturitas. 1982 Dec;4(4):325-32.
The production and aromatization of dehydroepiandrosterone in post-menopausal women.

Longcope C, Bourget C, Flood C.

Using infusions of [3H]dehydroepiandrosterone (DHEA) and [14C]oestrogens, the metabolic clearance rates (MCRD) and blood production rates (PDB) of DHEA and the rate of aromatization of DHEA to oestrone and oestradiol were measured in 7 normal post-menopausal women. The mean +/- SEM value for MCRD was 1850 +/- 270 l/day and for PDB was 3.2 +/- 0.6 mg/day. The MCRD value is similar to those reported for young women but PDB is less than those reported for younger women. The mean +/- SEM value for the aromatization rate of DHEA to E1 in 6 women was 0.0058 +/- 0.004 and in 1 woman the aromatization rate of DHEA to E2 was 0.0008. About 30% of the aromatization of DHEA to E1 occurred via the blood pool of androstenedione. However, 20-25% of E1 arose via the aromatization of DHEA to E1 in peripheral tissues without the intermediacy of the blood pool of androstenedione, and thus the peripheral aromatization of DHEA can be an important source of E1 in some women.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6221177&dopt=Abstract DHEA




Horm Res. 1983;18(4):175-85.
Plasma levels of androgens and 17 alpha-OH-progesterone as an index of the adequacy of treatment in congenital adrenal hyperplasia.

Ilondo MM, Vanderschueren-Lodeweyckx M, Pizarro M, Vlietinck R, Malvaux P, Eggermont E, Eeckels R.

Plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA), delta 4-androstenedione (delta 4), testosterone and 17 alpha-OH-progesterone (17-OH-P) were studied in 58 samples collected in 18 patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, during long-term ambulatory treatment with hydrocortisone. At each visit the patients were classified as being either in good control (GC) or in poor control (PC), based on well-defined clinical, auxological and biochemical criteria. The results were analyzed in relation to the degree of control and to chronological age (CA), bone age (BA), body surface (BS) and pubertal development. The most clear distinction between the children with GC and those with PC is found for DHEA-S (p less than 0.001 for BA). The majority of the DHEA-S values in the children with GC are closely grouped and significantly below the normal limits for CA, BA, BS and pubertal stage (p less than 0.001). In contrast, the PC children have wide-spread values, most of them being within or above the normal limits. The difference between GC and PC is also significant for testosterone (p less than 0.01) and delta 4 (p less than 0.05), but not for DHEA. Of the five steroids studied, DHEA-S is the most specific, whereas testosterone is the most sensitive and especially useful in girls and in prepubertal boys. delta 4 and 17-OH-P are almost as sensitive as DHEA-S, but they are less specific. DHEA is the less valid criterium.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6227545&dopt=Abstract DHEA




Diabetes. 1984 Jan;33(1):26-32.
Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice.

Coleman DL, Schwizer RW, Leiter EH.

Dehydroepiandrosterone (DHEA) was fed at 0.1-0.4% in the diet to genetically diabetic (db/db) or obese (ob/ob) C57BL/KsJ (BL/Ks) or C57BL/6J (BL/6) mice. Treatment of BL/Ks-db/db or ob/ob mice with 0.4% DHEA prevented hyperglycemia, islet atrophy, and severe diabetes associated with this inbred background, but did not affect weight gain and food consumption. Homozygous obese (ob) or diabetes (db) mice on the BL/6 background were more sensitive to DHEA, and the mild, transient hyperglycemia associated with ob or db gene expression on the BL/6 inbred background could be prevented by 0.1% DHEA. Both body weight and food consumption were decreased in BL/6 mutants maintained on 0.1% DHEA whereas this effect was not seen in BL/Ks mutants fed up to 0.4% DHEA. Early therapy with 0.4% DHEA, initiated at 2 wk of age, prevented the development of most diabetes symptoms and decreased the rate of weight gain in pups of all genotypes. In addition to therapeutic effects on both obese mutants, DHEA effected significant changes in an aging study using normal BL/6 female mice. Four weeks of DHEA treatment initiated at 2 yr of age improved glucose tolerance and at the same time reduced plasma insulin to a "younger" level. This suggests that DHEA may act in insulin-resistant mutant mice and in aging normal mice to increase the sensitivity to insulin.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6228478&dopt=Abstract DHEA