Characterization of oviductal aromatase in the northern leopard frog, Rana pipiens.

Previous work has shown that the oviduct of the northern leopard frog, Rana pipiens, can convert testosterone to estradiol. The present paper examines the characteristics of the aromatase responsible for this reaction and compares it with human placental aromatase. Microsomes were isolated from the oviducts, and aromatase activity was assayed by a tritiated water release method.

Induction of tamoxifen-dependent rat mammary tumors.

We have observed previously that animals given tamoxifen (TAM) and the carcinogen dimethylbenzanthracene develop exclusively hormone-independent tumors. Since our data implied that the TAM-associated tumors were different from control tumors, we undertook studies to examine the role of TAM in the induction and growth of these tumors. Following cessation of TAM administration, almost one-third [29.

Inhibition of growth and appearance of estrogen-dependent rat mammary tumors by 10-propargylestr-4-ene-3,17-dione, an aromatase inhibitor.

The aromatase inhibitor 10-propargylestr-4-ene-3,17-dione (PED) has been evaluated in vivo as an anticancer agent. Prolonged administration of PED to rats bearing dimethylbenzanthracene-induced mammary tumors resulted in significant regression of hormone-responsive tumors within several days. Greater than 50% regression was generally observed after 14 days of treatment, irrespective of dose (1, 5, or 50 mg/kg body weight/day).

Role of tamoxifen in the induction of hormone-independent rat mammary tumors.

Using the dimethylbenzanthracene-induced rat mammary tumor model, we examined the appearance and growth of tumors in animals given tamoxifen (TAM) either coincident with dimethylbenzanthracene or after initial tumor formation. While fewer tumors arose after coadministration of antiestrogen and carcinogen and TAM treatment caused regression of most existing tumors, new tumors developed in the presence of TAM in both studies. Since none of these new tumors regressed following ovariectomy, all were classified as hormone independent.

Effect of 4-hydroxyandrostenedione on murine Leydig tumor cell steroidogenesis.

The murine Leydig cell tumor (M5480A) possesses high levels of estrogen receptor and is known to produce estrogens. In these studies we examined the effects of the potent aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) on Leydig tumor cell steroidogenesis both in vitro and in vivo. The addition of 4-OHA to Leydig tumor cells in primary culture resulted in a dose- and a time-dependent decrease in media progesterone levels.

Immunocytochemical localization and enzymatic distribution of rat ovarian aromatase.

A rabbit antiserum directed against purified human placental aromatase was used for immunohistochemical localization of the enzyme in rat ovaries. Immunostaining was conducted on tissue from animals at various ages and in different reproductive states: immature; immature, eCG-treated; immature pseudopregnant; adult cycling; and adult pregnant. Various labeling protocols were employed (e.

Ovarian contents of immunoreactive beta-endorphin and alpha-N-acetylated opioid peptides in rats.

beta-Endorphin was measured by radioimmunoassay in homogenates of ovaries from immature Sprague-Dawley rats (21-29 days of age) and found to be present at levels of about 0.6-0.7 ng/ovary.

A long-acting gonadotropin-releasing hormone agonist inhibits the growth of a human ovarian epithelial carcinoma (BG-1) heterotransplanted in the nude mouse.

Human ovarian epithelial carcinoma (BG-1) was heterotransplanted in female nude athymic mice and growth was evaluated in intact, surgically castrated, and gonadotropin-releasing hormone (GnRH) agonist (Lupron-SR)-treated mice. Tumor volume was represented as percent of tumor volume on day 0 and measured every other day from the administration of drug and/or the attainment of a minimum tumor volume of 0.5 cm3 on each side of the animal.

Divergence between ovarian aromatase activity, estrogen, and androgen levels in the cycling rat.

Serum estrogen levels vary in a cyclic fashion during the rat estrous cycle, reaching peak values on proestrus and then rapidly declining. Daily measurements of ovarian aromatase activity appear to follow a similar pattern, suggesting a potential regulatory role for the enzyme. To examine this hypothesis, mature rats were killed at various times, and ovarian microsomes were assayed for aromatase activity, while androstenedione, testosterone, estradiol, and estrone levels were measured in ovarian cytosol by RIA.

The effects of in vivo administration of 10-propargylestr-4-ene-3,17-dione on rat ovarian aromatase and estrogen levels.

We have previously demonstrated that 10-propargylestr-4-ene-3,17-dione (PED) functioned as an irreversible inhibitor of rat ovarian aromatase in vitro. These studies were undertaken to examine the in vivo effects of PED on rat ovarian aromatase activity and estrogen production. In the current experiments, a single injection of PED (0.

Endocrine characterization of a human ovarian carcinoma (BG-1) established in nude mice.

The steroid receptor-positive human ovarian cancer (BG-1) was evaluated to determine its usefulness as a tumor model. This tumor grows in intact male and female nude mice without hormone supplements. Moreover, its growth was significantly accelerated in ovariectomized mice, and the increased growth rate could be reversed by estradiol administration.

Characterization of pregnant mare's serum gonadotropin-stimulated rat ovarian aromatase and its inhibition by 10-propargylestr-4-ene-3,17-dione.

Aromatase, the important regulatory enzyme that converts androgens to estrogens, is found in relatively high levels in the human placenta. However, since the ovary is the major source of the estrogens in females, we undertook studies to compare the rodent ovarian enzyme with that from human placenta. Pregnant mare's serum gonadotropin (PMSG) markedly increases aromatase activity in the ovaries of immature rats, and this model was used in order to reproducibly obtain high enzyme levels.

Inhibition of aromatase activity and of endocrine-responsive tumor growth by 10-propargylestr-4-ene-3, 17-dione and its 17-propionate derivative.

Two androstenedione derivatives, 10-propargylestr-4-ene-3,17-dione and its 17-propionated form, were administered to normal cycling rats, and both compounds led to an inhibition of ovarian aromatase. Under in vitro conditions, only the former compound exhibited high potency as an inhibitor of rat ovarian and human placental microsomal aromatase. At 1 mg/kg/day both compounds were effective in promoting regression of 9,10-dimethyl-1,2-benzanthracene-induced mammary tumors in rats without terminating their estrous cycle.

Inhibition of Leydig tumor cell steroidogenesis by 10-propargylestr-4-ene-3,17-dione, an irreversible aromatase inhibitor.

The murine Leydig cell tumor (M5480A) was assayed for the presence of aromatase activity and for the effects of 10-propargylestr-4-ene-3,17-dione (PED), an aromatase inhibitor, on steroidogenesis. Microsomal preparations from these tumors contained low levels of aromatase activity which was PED sensitive. In addition, these Leydig tumor cells were maintained in primary culture and incubated under basal and gonadotropin-stimulated conditions with various doses of PED.

Induction of an estrogen-dependent early steroidogenic lesion in murine Leydig tumor cells.

The effects of low doses (37 pM to 3.7 nM) of 17 beta-estradiol on Leydig tumor cell steroidogenesis were studied in primary culture. This gonadotropin-responsive Leydig tumor line (M5480A) produces progesterone as the major steroid and lower levels of testosterone.

Intracellular metabolism of hCG.

After administration of hCG, hormone enters pseudopregnant rat ovarian cells rapidly. Although evidence for small amounts of hCG bound to receptor exists within cells, the major fraction of internalized hCG is free and not receptor bound. The intracellular site of dissociation of hCG from its receptor is unknown.

Divergent effects of phenothiazines on Leydig tumor cell steroidogenesis and adenylate cyclase activity.

The dose and temporal (1-24 h) effects of two phenothiazines, chlorpromazine and trifluoperazine, on steroidogenesis and adenylate cyclase activity of gonadotropin-responsive Leydig tumor cells (M5480A) in primary culture were examined. At low doses (e.g.

Fate of human chorionic gonadotropin bound to rat corpora lutea.

The current studies were designed to ascertain the fate of hCG bound to rat corpora luteal cell receptors. Graded doses of highly purified hCG (CR119), ranging from 0.1-10.