The influence of cortisol on estrogen synthesis by the bovine placenta and the importance of the delta 4 and delta 5 pathway for estrogen production were investigated. For experiment 1, portions of fetal villi (200 mg) were incubated for 48 hours with 0, 10, 100, and 1,000 ng of cortisol/ml with [3H]androstenedione (3H-A) or [3H]pregnenolone (3H-P5). Villi were also incubated for 4, 28, and 52 hours with or without cortisol (500 ng/ml) and with 3H-A or 3H-P5 (experiment 2). The conversion of various [3H]steroid metabolites such as A, P5, 17 alpha-OH-pregnenolone (17 alpha-OH-P5), progesterone (P4), 17 alpha-OH-P4, cholesterol (chol), and chol plus lipoprotein (500 micrograms/ml) into estrogen was measured during a 4-hour incubation (experiment 3). In experiment 1, cortisol increased conversion of 3H-A and 3H-P5 into estrogen by 3 to 41% and 7 to 34%, respectively, in a dose-dependent manner (P < 0.05). In experiment 2, times of incubation did not influence conversion of 3H-A into estrogen, which, however, was increased significantly (P < 0.05) over all times of incubation by administration of 500 ng of cortisol/ml. Conversion of 3H-P5 into estrogen increased over time of incubation and was stimulated by cortisol (P < 0.05). However, there was no interaction between cortisol treatment and time of incubation. In experiment 3, conversion of 3H-A, 3H-P5, and 3H-17 alpha-OH-P5 into estrogen was greater than the conversion of the other precursors tested. Mean conversion of 3H-A, 3H-P5, 3H-17 alpha-OH-P5, 3H-P, 3H-17 alpha-OH-P4, 3H-chol, and 3H-chol plus lipoprotein was 23%, 10.6%, 11.0%, 1.8%, 1.8%, 0.3% and 0.7%, respectively. Our results suggest that, in cows, the delta 5 pathway is the preferred pathway for placental estrogen synthesis and that cortisol directly stimulates estrogen production, probably by activating enzymes involved in this pathway.

Objective—To investigate the in vitro effect of the combination of lignan enterolactone (ENL) or lignan enterodiol (END) with melatonin on steroid hormone secretion and cellular aromatase content in human adrenal carcinoma cells. Sample—Human adrenocortical carcinoma cells. Procedures—Melatonin plus ENL or END was added to cell culture medium along with cAMP (100μM); control cells received cAMP alone. Medium and cell lysates were collected after 24 and 48 hours of cultivation. Samples of medium were analyzed for progesterone, 17-hydroxyprogesterone, androstenedione, aldosterone, estradiol, and cortisol concentration by use of radioimmunoassays. Cell lysates were used for western blot analysis of aromatase content. Results—The addition of ENL or END with melatonin to cAMP-stimulated cells (treated cells) resulted in significant decreases in estradiol, androstenedione, and cortisol concentrations at 24 and 48 hours, compared with concentrations in cells stimulated with cAMP alone (cAMP control cells). The addition of these compounds to cAMP-stimulated cells also resulted in higher progesterone and 17-hydroxyprogesterone concentrations than in cAMP control cells; aldosterone concentration was not affected by treatments. Compared with the content in cAMP control cells, aromatase content in treated cells was significantly lower. Conclusions and Clinical Relevance—The combination of lignan and melatonin affected steroid hormone secretion by acting directly on adrenal tumor cells. Results supported the concept that this combination may yield similar effects on steroid hormone secretion by the adrenal glands in dogs with typical and atypical hyperadrenocorticism.

Objective: To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination. Animals: 20 female Japanese quail. Procedures: Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy. Results: Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. Plama androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group then in the control group. Conclusions and Clinical Relevance: 4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.