Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperprolactinemia has been associated with several reproductive disorders. To investigate whether hyperprolactinemia directly affects rat ovarian function, we examined the ovarian histopathology and the activities of the four ovarian enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase in hyperprolactinemic rats and controls. Hypophysectomized, gonadotropin-treated Fisher rats were made hyperprolactinemic by isografting pituitary glands under the kidney capsule. The control animals received skeletal muscle. The ovaries were resected, pooled according to prolactin levels and microsomal enzyme activities were measured from each pool. Prolactin (PRL) levels were 344 +/- 23 ng/ml in the hyperprolactinemic rats and 18 +/- 5 ng/ml in the controls (p less than 0.001). Estradiol concentrations were 609 +/- 47 pg/ml in the hyperprolactinemic animals and 56 +/- 13 pg/ml in the controls (p less than 0.001). Ovarian and uterine weights were significantly higher in the hyperprolactinemic rats (p less than 0.02). Ovarian histopathology demonstrated benign polycystic transformation in the hyperprolactinemic animals. Hyperprolactinemia had no effect on 3 beta-HSD, but was associated with significant decreases in the 17-OH, 17,20-D and aromatase activities when compared to controls (p less than 0.001). We conclude that prolactin has a direct effect on rat ovarian function which appears to be independent of changes in gonadotropin secretion.
Steroids 1984 Jun
PMID:The effects of prolactin on rat ovarian function. 633 28

The luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH (LHRHa) inhibits rat testicular testosterone secretion. To determine whether LHRHa decreases serum testosterone concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly testicular testosterone biosynthesis, we examined the effects of LHRHa on the activities of 5 key testicular steroidogenic enzymes. Thirty hypophysectomized, hOG treated rats were given either LHRHa (1 micrograms sc/day) or saline during 7 days. The LHRHa treated animals exhibited a significant decrease of serum testosterone when compared to the control group (498 +/- 37 ng/dl vs 2044 +/- 105 ng/dl, mean +/- SEM, P less than 0.001). 17-Hydroxyprogesterone serum levels were also decreased in the LHRHa treated rats (61 +/- 6 ng/dl vs 93 +/- 7 ng/dl, P less than 0.005), while serum progesterone levels were similar in both groups of animals. These changes in steroid concentrations were associated with decreases in the microsomal enzyme activities of 17-hydroxylase (37 +/- 9 vs 654 +/- 41 pmol/mg protein/min, P less than 0.001), 17,20-desmolase (103 +/- 9 vs 522 +/- 47 pmol/mg protein/min, P less than 0.001), 3 beta-hydroxysteroid dehydrogenase (1.7 +/- 0.02 vs 4.1 +/- 0.1 nmol/mg protein/min, P less than 0.001), aromatase (95 +/- 7 vs 228 +/- 6 pmol/mg protein/min, P less than 0.001) and 17-ketosteroid reductase (167 +/- 9 vs 290 +/- 18 pmol/mg protein/min, P less than 0.01) in the LHRHa treated animals. These findings indicate that LHRHa can inhibit directly rat testicular testosterone biosynthesis.
Steroids 1984 Feb
PMID:Direct effect of the luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH on rat testicular steroidogenesis. 639 51

The production of progesterone, estrogen and androgen as well as the metabolism of radiolabelled progesterone by various cellular components of rat ovarian follicles were studied. Granulosa (G), theca (T), recombined granulosa plus theca (G+T) and intact follicular wall (FW) of ovaries from immature rats treated with pregnant mare serum gonadotropin (8 IU) were cultured for 24 h in the presence or absence of [4-14C]progesterone. The estrogen and androgen accumulation when calculated per follicle was several fold greater in FW than in G, T, or G+T preparations. The conversion of radiolabelled progesterone to its identified C21 catabolites (20 alpha-hydroxy-4-pregnen-3-one and 3 alpha-hydroxy-5 alpha-pregnan-20-one) was significantly lower in FW than in G+T incubations. Conversely, the metabolism of radiolabelled progesterone to androsterone was several fold greater in FW than in G+T incubations. Addition of hydroxyflutamide to FW incubations significantly decreased estrogen production and increased the conversion of radiolabelled progesterone to androsterone. Estrogen production by follicular wall may be enhanced by androgenic stimulation of aromatase activity as well as by a structure-dependent factor(s) of a yet unknown nature, both of which may decrease progesterone catabolism to biologically inactive progestins while promoting progesterone conversion to androgens and eventually to estrogens.
Steroids 1984 Oct
PMID:Steroidogenic capabilities of various compartments of rat ovarian follicles in culture. 654 71

[1 beta-3H], [1 alpha,2 alpha-3H] and [1 beta,2 beta-3H] 4-Hydroxyandrostenedione (4-OH-A) were synthesized to study the mechanism of inhibition of aromatase by 4-OH-A. Incubations of [1 beta-3H] and [1 beta,2 beta-3H] 4-OH-A with placental microsomes in the presence of NADPH showed very little loss of tritium, with aromatization of 4-OH-A ranging from 0.3 to 0.6 percent. No loss of tritium was observed in the absence of NADPH. The extent of covalent binding of 4-OH-A to microsomal proteins was higher with incubations in the absence of NADPH than with those in the presence of NADPH. These results are discussed in light of what has been proposed for the mechanism of androgen aromatization.
Steroids 1983 Jun
PMID:Studies on the mechanism of action of the aromatase inhibitor, 4-hydroxyandrostenedione. 666 21

Immature hypophysectomized rats were injected with PMS; some groups received hCG 48h later. The C17,20-lyase activity in the granulosa cells removed from the large preovulatory follicles was estimated by the amount of labelled acetic acid produced from 21 (14C) progesterone or 17-hydroxyprogesterone. 17 alpha-hydroxylase and aromatase activity were measured by the tritium exchange method. Although the granulosa cells contained lyase, it was considerably less than their hydroxylase activity. The remaining tissue, consisting of small follicles and hypertrophied thecal and interstitial tissue, had a great deal more lyase and hydroxylase activity than did the granulosa cells. The results are consistent with the view that granulosa cells can produce estrogen from progesterone and do not require androgen precursors from the theca and/or interstitium.
Steroids 1983 Nov
PMID:The C17,20-lyase, 17 alpha-hydroxylase and aromatase activity in rat ovarian granulosa cells stimulated in vivo by gonadotropins. 668 Sep 30

Immature hypophysectomized rats were injected with 2mg of diethylstilbestrol to increase granulosa cell numbers and with 20 IU of PMS to stimulate ovarian growth. Steroid 17 alpha-hydroxylase activity of cultured granulosa cell, harvested from mature follicles 48 h after injection of PMS, was demonstrated using a tritium exchange assay with 17 alpha 3H-pregneneolone as substrate. For comparison, aromatase activity of the same cells was examined by a similar assay using 1 beta 3H-testosterone as the substrate. The activities of the two enzymes were similar when expressed in terms of the amount of substrate converted per unit time. While an NADPH generating system in the incubation medium was essential for demonstrating any hydroxylase activity, 10-15% of the total aromatase activity could be found without added cofactor. Attempts to alter hydroxylase activity of granulosa cells by inclusion of LH, FSH or prolactin in the incubation medium were unsuccessful. However, activity could be change by prostaglandins (PG) or agents which can alter PG synthesis. Activity was increased by low concentrations of phospholipase A2 (PLA2), histamine, and arachidonic acid (AA). Large doses of PLA2, or AA, were inhibitory. PGE2, but not PGF2 alpha, increased, while indomethacin decreased, hydroxylase activity. The results clearly indicate that granulosa cells in the rat have a potent 17-hydroxylase system and therefore do not support the widely held contention that lack of this enzyme is one of the bases for the need for two kinds of cells for ovarian estrogen production.
Steroids 1981 Nov
PMID:Steroid 17 alpha-hydroxylase activity of ovarian granulosa cells from hypophysectomized immature rats treated with pregnant mare's serum gonadotropin (PMS). 679 17

Various C19-steroidal derivatives have been synthesized and evaluated in biochemical assays for their ability to inhibit the biosynthesis of estrogens. Steroids with substitutions on the A or B ring were prepared by Michael addition of various thiol reagents to appropriate dienone intermediates. An in vitro assay using human placental microsomes was used to evaluate aromatase-inhibitory properties. Synthesized compounds that exhibited high inhibitory activity were further evaluated under initial velocity conditions to determine apparent Ki values. Several 7 alpha-substituted androstenediones were effective competitive inhibitors and have apparent Ki values ranging from 18 to 69 nM, with the apparent Km for androstenedione being 63 nM. The most effective competitive inhibitor tested is 7 alpha-(4'-amino)phenylthioandrost-4-ene-3,17-dione with an apparent Ki of 18 nM. Derivatives of this 7 alpha-thioether compound that contain alkylating moieties have been prepared as potential irreversible enzyme inhibitors and demonstrate varying abilities to inactivate the aromatase enzyme. The results of these studies demonstrate that large chemical functionalities such as an aromatic ring with polar substituents can be accommodated in or near the active site of aromatase and, in some cases, can enhance the affinity of the enzyme for the inhibitors.
 ...
PMID:Substituted C19 steroid analogs as inhibitors of aromatase. 708 96

The 7 alpha-ethyl,propyl,butyl,3'-t-butoxypropyl,allyl,3'-hydroxypropyl 17-acetate, and 3'-chloropropyl 17-acetate derivatives of testosterone and the 7 alpha-3'-t-butoxypropyl, 3'-hydroxypropyl,3'-acetoxypropyl,3'-bromoacetoxypropyl, 3'-chloropropyl, and 2'-oxo-3'-bromopropyl derivatives of 4-androstene-3,17-dione were synthesized. The testosterone derivatives were found to lose androgenic and anabolic activity rapidly as the size of the group at the 7 position increased. Many of the compounds were tested as inhibitors of aromatase. The 17-keto compounds were more active than the corresponding alcohols and the enzyme was found to tolerate at least the bulk of a hydroxypropyl group at the C-7 alpha position.
Steroids 1982 Dec
PMID:7 alpha-Alkyltestosterone derivatives: synthesis and activity as androgens and as aromatase inhibitors. 718 11

Several 7 alpha-substituted 4-androstene-3,17-diones are potent inhibitors of the biosynthesis of estrogens, with the most effective being 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione. An azide derivative of this 7 alpha-thioether compound has been prepared as a potential photoaffinity inhibitor. The enzyme kinetics of the azide analog were examined under both dark conditions and UV irradiation. In the dark, the azide was a very potent competitive inhibitor, with an apparent Ki of 1.3 nM. Under UV-irradiation, a time-dependent loss of aromatase activity was also observed. These studies indicate that the 7 alpha-substituent enhances the affinity of the steroidal analogs for the enzyme site.
Steroids 1982 Dec
PMID:A photoaffinity inhibitor of aromatase. 718 16

The ability of isolated large or small bovine luteal cells to synthesize estradiol-17 beta was tested by incubations in the absence or in the presence of exogenous testosterone. Using a specific radioimmunoassay, no synthesis of estradiol-17 beta could be detected in the small or large luteal cells after incubation in the absence of testosterone. However, after incubation in the presence of exogenous unlabelled testosterone, radioimmunoassay data suggested the existence in the large but not the small luteal cells of synthesis of estradiol-17 beta. However, the results obtained by measuring the conversion of 3H-testosterone to 3H-estradiol-17 beta by cocrystallization with unlabelled estradiol-17 beta failed to confirm the presence of aromatase in the large cells. These data indicate that aromatization in large and small bovine luteal cells is probably negligible. Moreover, they cast serious doubt on studies of aromatization in luteal tissue based on radioimmunoassay data only.
Steroids 1981 Sep
PMID:Aromatization of testosterone in large and small bovine luteal cells. Conflicting results between radioimmunoassay and cocrystallization data. 730 33


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