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At least 163 records · Page 9Linked to original sources
PubMed1975

Antagonism by dibutyryl adenosine cyclic 3',5'-monophosphate and testololactone of concanavalin A capping.

Exposure of CHO-K1 cells in vitro to dibutyryl adenosine cyclic 3',5'-monophosphate (DBcAMP) plus testololactone produces a rapid, reversible antagonism of ligand-induced collection of initially dispersed concanavalin A (Con A) binding sites into a caplike mass. Morphologically, as Con A capping occurs, the cells become less spread and then round completely. With prolonged Con A exposure, cells cultured in either the absence or the presence of DBcAMP plus testololactone cap and round. Capping is blocked by cold treatment and respiratory inhibitors. Colcemid at concentrations greater than 1 muM promotes both Con A capping and cell rounding. Cytochalasin B at similar concentrations inhibits both capping and cell rounding. Treatment of cells with Con A has little effect on intracellular cAMP concentration. Possible mechanisms by which cAMP may modulate the movement of Con A binding sites are discussed.

Animals↗
PubMed1986

Studies on steroid monooxygenase from Cylindrocarpon radicicola ATCC 11011. Oxygenative lactonization of androstenedione to testololactone.

A steroid monooxygenase of Cylindrocarpon radicicola was found to catalyze oxygenative lactonization of 17-ketosteroid, androstenedione, to yield D-homo-17 alpha-oxasteroid, testololactone, i.e., the androstenedione monooxygenase reaction, in addition to catalyzing the progesterone monooxygenase reaction. The reaction product was identified by TLC, GLC, and mass spectrometry. The oxygenation proceeded with unitary stoichiometry for 17-ketosteroid, NADPH, and molecular oxygen, indicating that it is a typical monooxygenase reaction of the external electron donor type. The enzyme catalyzed successively the side chain cleavage reaction of 17 alpha-hydroxy-20-ketosteroid to produce its 17-keto derivative and the lactonization of the product. The effects of pH and of the concentration of substrate steroids on the androstenedione monooxygenase reaction were different from those on the progesterone monooxygenase reaction. Progesterone is a strong and competitive inhibitor of the lactonization of 17-ketosteroids. The steroid monooxygenase is concluded to have the activities of both oxygenative esterification of 20-ketosteroids and oxygenative lactonization of 17-ketosteroids.

Androstenedione↗
PubMed1975

Treatment of intra-abdominal and abdominal wall desmoid tumors with drugs that affect the metabolism of cyclic 3',5'-adenosine monophosphate.

A female patient with Gardner's syndrome was treated with delta1-testololactone (200 mg daily) because of growth of a large desmoid tumor in the pelvis and lower abdomen and a tumor in a scar from a previous laparotomy. There was also pain and swelling of the left leg. An immediate effect of the drug therapy was complete relief of pain followed shortly thereafter by disappearance of the edema of the leg. After two months, the numerous sebaceous cysts were less prominent. The gross measurements of the diameter of the pelvic and lower abdominal tumor clearly demonstrated tumor shrinkage following therapy. Small polyps scattered over the rectal mucosa and numerous osteomata were not demonstrably affected. After one year of treatment with delta1-testololactone, a laparotomy for partial small bowel obstruction was necessary. Obstruction was caused by the involvement of small bowel mesentery and the bowel itself in a contracted residuum of dense fibrous tissue. Substitution of theophylline and chlorothiazide for the testololactone in Januray 1974 was followed by further diminution of the measurable abdominal and pelvic desmoids. All of these compounds synergize the action of 3',5'-adenosine monophosphate and at least the latter two may function by inhibiting the action of 3',5'-adenosine monophosphate diesterase.

Abdominal Muscles↗
PubMed1988

Hormonal abnormalities in obesity.

We have found a number of interesting hormonal abnormalities in obese men and women: 1) Obese women have normal levels of estrone, total estradiol, and total testosterone, but as a consequence of their subnormal levels of SHBG, their levels of free estradiol and free testosterone are significantly elevated. 2) Massive weight loss in obese women (to still elevated weight) results in normalization of the previously elevated free estradiol and free testosterone. 3) Obese women have normal plasma DHEA levels, but a significant, age-invariant decrease of the plasma DHEA/T ratio, which could be due to increased tissue activity of 3 beta-hydroxysteroid dehydrogenase. 4) Massive weight loss produces an age-dependent effect on DHEA levels in obese women: the levels increase to supranormal values in women around age 20, with diminishing increases at higher premenopausal ages and no increase at all at perimenopausal age. 5) Obese men have elevated levels of estrone and both free and total estradiol, and subnormal levels of free and total testosterone and of FSH; all these abnormalities are proportional to the degree of obesity. They also have relatively subnormal LH levels, i.e. normal in the face of hypotestosteronemia. The combination of these findings represents a state of mild hypogonadotropic hypogonadism (HHG), which we believe to be induced by the hyperestrogenemia. 6) Normalization of the estrogen levels of obese men, by suppression of adrenocortical secretion of aromatase substrates or by inhibition of aromatase, tends to normalize the HHG. 7) Massive weight loss in obese men normalizes their HHG without any decrease in plasma estrogen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Hydrotestolactone lowers serum oestradiol and PRL levels in normal men: evidence of a role of oestradiol in prl secretion.

The effect on serum PRL levels of lowering serum oestradiol (E2) concentration by short-term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E2 levels decreased from 68 +/- 5.8 to 26 +/- 2.5 pmol/l (mean +/- SE, P less than 0.05). These E2 changes were accompanied by a significant decrease in mean 2-h PRL levels from 11.2 +/- 2.1 to 6.5 +/- 1.6 ng/ml mean +/- SE, P less than 0.05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E2 may be one of the factors which control blood PRL concentrations in men.

Adult↗
PubMed1986

Enzymatic control of estrogen production in human breast cancer: relative significance of aromatase versus sulfatase pathways.

One-third of the cases of breast cancer in postmenopausal women are hormone-dependent and the lesions regress upon treatment with antiestrogens or inhibition of estrogen biosynthesis. In these patients, estrogens are synthesized in extraglandular tissues from adrenal precursors and re-enter plasma to produce estrone levels of 52 +/- 6.5 pg/ml (mean +/- SEM) and estradiol concentrations of 13.1 +/- 0.7 pg/ml. However, the fact that the levels of estrogen in breast tumor tissue are an order of magnitude higher than plasma levels suggested the possibility of in situ estrogen production. To address this possibility, we measured several enzymes involved in estradiol biosynthesis in human tumors. Forty-eight of 61 tumors contained aromatase (estrogen synthetase) activity ranging from 5-80 pg/gm protein per hour. By comparison, the levels of estrone sulfatase were 10(6) higher, ranging from 0.8-125 micrograms/gm protein per hour. Because the sulfatase enzyme was of lower affinity (i.e., Km = 27 microM) than that of aromatase (i.e., 0.027 microM), the amount of estrogen formed under conditions of similar substrate concentrations was compared and found to be 10-fold higher via the sulfatase enzyme. In 41 additional tumors, the 17 beta-hydroxysteroid dehydrogenase enzyme, catalyzing the conversion of estrone to estradiol, was uniformly present. To test the biologic relevance of the estrone sulfate to estrone to estradiol pathway, estrogen-dependent nitrosomethylurea rat mammary tumors were grown in soft agar in the presence of estrone sulfate. Concentrations of estrone sulfate of 10(-6) microM significantly (p less than 0.01) stimulated colony formation in this system in which 75.5-98.6% of estrone sulfate was converted to estrone and 0.2 to 6% to estradiol. These data support the hypothesis that mammary carcinomas can synthesize estradiol in situ from circulating estrogen precursor and that local conversion is biologically important. On the basis of comparative data, the estrone sulfate to estrone to estradiol pathway is quantitatively more important than that involving androstenedione to estrone to estradiol.

17-Hydroxysteroid Dehydrogenases↗
PubMed2002

Cyclic AMP and the reverse transformation reaction.

Traditional methods for cancer treatment have been aimed at killing the cancer cells. Unfortunately this approach all too often is accompanied by harmful killing of normal cells. The present paper describes an experimental program in our laboratory in which cancer cells are treated so as to revert to normal cell behavior. This process, which we have named reverse transformation, appears to offer considerable hope in the treatment of a large number of malignancies.

Animals↗
PubMed1978

[Androgen therapy of incurable breast neoplasms. Controlled clinical study: nandrolone-testololactone-drostanolone].

In 91 patients with advanced breast cancer testololactone, drostanolone, and nandrolone were compared in a controlled clinical trial. Remissions were registered after 4 weeks and after another 12 week period; during this second interval the patients received an additional treatment with cyclophosphamide. There was no difference in the effectivity between the three drugs. Remission rate was in average after 4 weeks 24% and after 16 weeks 46%.

Androstanols↗
PubMed1987

Effect of aromatase inhibitors on the histology of the cycling rat ovary.

Two aromatase inhibitors, 4-hydroxyandrostenedione (4-OHA) and testololactone (Teslac), were tested to determine their effects on folliculogenesis, particularly ovarian histologic alterations, in the cycling rat. Adult, female Sprague-Dawley rats were treated with continuous infusion of both inhibitors at concentrations of 10(-8), 10(-4), and 10(-2) M for 30 days. The effect of the inhibitors on cultured granulosa cells harvested on proestrus was determined in vitro. The in vivo administration of each inhibitor induced significant reduction in ovarian-vein estradiol levels. Estradiol synthesis in cultured granulosa cells was inhibited by both aromatase inhibitors in a dose-dependent fashion. These observations indicate that 4-OHA and Teslac significantly inhibit basal estradiol synthesis in vivo and in vitro. This effect on estrogen synthesis was not reflected in alteration of the ovarian histology in the cycling rat.

Androstenedione↗
PubMed1987

Enhancement of the hypertensinogenic action of 19-hydroxyandrostenedione by aromatase inhibitor, delta 1-testololactone.

To evaluate the enhancing effects of 1,2-dehydrotestololactone (delta 1-testololactone) on the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-A-dione), 1 mg 19-OH-A-dione, 10 mg delta 1-testololactone, or a combination of 1 mg 19-OH-A-dione and 10 mg delta 1-testololactone was injected into intact rats drinking water once a week for 4 weeks. The blood pressure of control rats and rats given 19-OH-A-dione, delta 1-testololactone, and a combination of 19-OH-A-dione and delta 1-testololactone in the fourth week was 130 +/- 2 (SE), 140 +/- 2, 128 +/- 6, and 152 +/- 5 mmHg, respectively. The blood pressure of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of control rats. In addition, the blood pressure of rats given a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of rats given 19-OH-A-dione alone. As delta 1-testololactone itself did not show any hypertensinogenic action, it is considered to enhance the hypertensinogenic action of 19-OH-A-dione. Although plasma 19-OH-A-dione concentrations of control rats and rats given delta 1-testololactone were lower than the sensitivity of RIA, those of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone were 116 +/- 3 and 222 +/- 37 pg/ml, respectively. Plasma 19-OH-A-dione concentrations of rats given a combination of 19-OH-A-dione and delta 1-testololactone were significantly higher than those of rats given 19-OH-A-dione alone. Therefore, delta 1-testololactone is considered to enhance the action of 19-OH-A-dione by increasing plasma concentrations of 19-OH-A-dione. As delta 1-testololactone is an aromatase inhibitor, the inhibition of the conversion of circulating 19-OH-A-dione to estrogens in peripheral tissues might be the cause of the elevation of plasma 19-OH-A-dione concentrations. These results indicate that aromatose inhibitors enhance the hypertensinogenic action of 19-OH-A-dione by decreasing the degradation of 19-OH-A-dione.

Androstenedione↗
PubMed2005

Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome.

PURPOSE: The aim of this study was to report the successful fertility treatment of men with Klinefelter syndrome using testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). METHODS: A total of 42 men with Klinefelter syndrome who underwent 54 TESE procedures were identified. Before TESE, patients with serum testosterone levels less than 15.6 nmol/liter were treated with an aromatase inhibitor. Sperm retrieval rates and results of ICSI, including fertilization and clinical pregnancy, were collected. RESULTS: Mean pretreatment FSH and testosterone levels were 33.2 IU/liter and 9.8 nmol/liter. During medical therapy, the mean testosterone level rose to 17.0 nmol/liter (P < 0.01). Spermatozoa were found during 39 microdissection TESE procedures, on the day before, or day of oocyte retrieval during a programmed in vitro fertilization cycle. The sperm retrieval rate was 72% (39 of 54) per TESE attempt, and 29 of the 42 different men (69%) had adequate sperm found for ICSI. Thirty-three in vitro fertilization cycles yielded embryos for transfer in the 39 (85%) cycles with sperm retrieved. Eighteen clinical pregnancies have resulted in 21 live births [18 of 39 (46%)]. All children had a normal karyotype. CONCLUSION: TESE/ICSI is a successful intervention for the majority of patients with azoospermia and Klinefelter syndrome. Sperm retrieval and ICSI success in men with Klinefelter syndrome are comparable with other men with nonobstructive azoospermia treated at our center.

Adult↗