Showing papers on "Steroid biosynthesis published in 1972"

Impotence and Diabetes: Studies of Androgenic Function in Diabetic Impotent Males

Abstract: Androgenic function was studied in seven diabetics with sexual impotence and in five patients with paraplegia. Plasma concentration of testosterone was measured before and after administration of 5,000 U. of human chorionic gonadotropin (HCG). Steroid biosynthesis by testicular tissue was studied in vitro and testicular morphology was evaluated by light and electron microscopy. The diabetic patients were also evaluated neurologically. Motor conduction velocity, electromyography of the quadriceps and the function of urinary bladder were studied. Plasma concentration of testosterone was in the normal range in basal conditions in impotent diabetics (mean 578 ± 234 mμg./100 ml.) and paraplegics (mean 788 ± 184 mμg./ 100 ml.). After stimulation with HCG, impotent diabetics showed a mean value of 1,523 ± 314 mμg./100 ml. In vitro steroid biosynthesis by testicular homogenates of diabetics and paraplegics was normal. The morphology of the interstitial tissue was normal in patients with diabetes or paraplegia. Subcellular characteristics of Leydig cells were also normal. In the tubules, a marked hypospermatogenesis with desquamation of the germinal epithelium was observed in the two groups in all patients. Alterations of the motility of the bladder were seen in six diabetics and all paraplegics. Motor conduction velocity was abnormal in the diabetics. It is concluded that in our patients androgenic function was normal, and therefare impotence can not be attributed to hormonal deficieney.

The Control of the Reptilian Gonad

Abstract: In reptiles, there is adequate evidence to indicate environmental control of the ovarian cycle through hvpothalamic pathways and the subsequent release of tropic hormone (s) from the anterior pituitary. The role of the pineal-parietal complex still remains to be elucidated. In the hypothalamus there appear to be steroid sensitive areas and both progesterone and estrogen appear to have important feedback influences upon gonadal growth ovulation, and ovarian steroid production. Cytological studies of the reptilian pituitary indicate similar cell types to those observed in mammalian pituitaries, but thus far, two gonadotrophs cannot be identified with any certainty. Chemical and biological studies of the action of mammalian gonadotropuis suggest that in reptiles hormones which are FSH-like in mammals are able to stimulate gonadal development, ovulation, and steroid biosynthesis under certain conditions. Preliminary studies of the chemistry of turtle gonadotropuis have so far demonstrated only one active principle, which is chemically similar to mammalian LH, but is far more active than the latter hormone in reptilian systems. Further, the hormone also has FSH-like activity in the reptile. Thus reptilian gonadal development can be stimulated by treatment with a variety of mammalian gonadotropins. Recent studies have indicited an important role for growth hormone, acting in concert with gonadotropin and estrogen in the regulation of vitellogenesis and ovarian growth. Piolactin appears to be an antigonadal agent in reptiles, as does progesterone. The exact manner in which these hormones exert their antigonadal action remains to be clarified, but at least one site of action is the central nervous system; other sites maybe the liver and the fat depot. Ovarian tissue from reptiles is able to synthesize and secrete steioid hormones by pathways similar to those present in mammalian ovaries. Circulating levels of estrogen have not been measured, but progesterone levels in the blood show distinct changes assocnted with pregnancy and the presence of corpora lutea in the ovary.

The development of smooth-surfaced endoplasmic reticulum in adrenal cortical cells of fetal guinea pigs.

Abstract: In most steroid-secreting cells smooth-surfaced endoplasmic reticulum is prominent. This organelle is a site of major enzymes involved in steroid biosynthesis. In fetal guinea pig adrenal cortical cells the development of tubular smooth-surfaced reticulum precedes all other apparent morphological changes at the cellular level, serving as the earliest indicator of structural differentiation. Its appearance coincides with the earliest evidence of steroid production by the adrenals (Ortiz et al., 1966). Further development and differentiation of this organelle in inner cortical cells gives rise to complex paracrystalline arrays. Subsequent segregation of cells containing these arrays to the deeper cortical regions, the deep zona fasiculata and zona reticularis, heralds the histological zonation of the cortex into three definitive regions. In the outer cortical cells of the developing zona glomerulosa, cisternal reticulum becomes prominent and in late fetal life large areas of the cisternal membranes become smooth-surfaced. Combined with information from bioassay experiments of Price and coworkers (Ortiz et al., 1966) the early appearance of the smooth reticulum supports the thesis that the adrenal is capable of steroid biosynthesis early in fetal development, before zonation of the cortex occurs. As the endoplasmic reticulum develops, polyribosomes become widely spaced on its surface. They may be involved in the synthesis and maintenance of the expanding smooth-surfaced reticulum and its associated steroidogenic enzymes, analogous to the development of smooth endoplasmic reticulum and associated enzymes in rat hepatocytes (Dallner et al., 1966a,b). The gradual confinement of cells containing paracrystalline arrays of smooth reticulum to the deep cortical zones implies functional significance for this compartmentalized form of endoplasmic reticulum.

Endogenous testosterone concentrations in rat testis interstitial tissue and seminiferous tubules during in vitro incubation.

Abstract: IT is generally accepted that, in the testis, the interstitial (Leydig) cell is the principal source of the steroid hormone testosterone and that this steroid plays an important but as yet undefined role in spermatogenesis. It has been suggested1 that the Sertoli cell of the seminiferous tubules may also produce steroid hormones, which may be involved in the control of spermatogenesis. The exact relative roles of the two types of cells in these respects are, however, unknown. Also, the endogenous concentrations of testosterone in either cell type have not been measured and it has yet to be demonstrated that the Sertoli cell is capable of de novo steroid biosynthesis.

Ultrastructural observations on possible sites of steroid biosynthesis in the ovarian follicular epithelium of two species of cichlid fish, Cichlasoma nigrofasciatum and Haplochromis multicolor.

Abstract: The follicular epithelial layers of the developing ovary of two cichlid species were examined by electron microscopy for evidence of steroid secretion. As each oocyte grew, its follicular cell layers increased in height, eventually becoming somewhat columnar; no development could be detected in follicle cells of non-activated oocytes. Isolated cells close to capillaries in the thecal layer developed large amounts of smooth membrane indicative of steroidogenesis, appearing similar at maturity to testicular Leydig cells. In Cichlasoma nigrofasciatum the mitochondria of differentiated thecal elements contained microtubule-like inclusions. It is suggested that these cells may produce estrogens during vitellogenesis.

The intermediary role of 5-pregnene-3β,20β-diol in the biosynthesis of 16-unsaturated C19 steroids in boar testis

Abstract: 1. The possible involvement of 5-pregnene-3beta,20beta-diol in 16-unsaturated C(19) steroid biosynthesis has been investigated. 2. 5,16-Androstadien-3beta-ol (andien-beta) formation from [4-(14)C]pregnenolone (3beta-hydroxy-5-pregnen-20-one), 5-pregnene-3beta,20alpha-diol and 5-pregnene-3beta,20beta-diol was studied in homogenates of boar testis and the mean yields obtained were 25.6, 2.7 and 16.0% respectively. 3. Short-term kinetic studies with pregnenolone and 5-pregnene-3beta,20beta-diol separately and together suggested that the latter compound might be an intermediate in the biosynthesis of andien-beta. 4. In agreement with this interpretation, radioactive 5-pregnene-3beta,20beta-diol has been isolated during andien-beta biosynthesis from [4-(14)C]pregnenolone in the presence of NADPH, more radioactivity being trapped under limiting conditions of andien-beta formation with NADH present as cofactor. 5. Further, 5-pregnene-3beta,20beta-diol and andien-beta have been shown to inhibit the formation of the 16-unsaturated C(19) steroid from [4-(14)C]pregnenolone, the yield of radioactive 5-pregnene-3beta,20beta-diol increasing in the presence of added unlabelled andien-beta. 6. It is concluded that there may be two pathways leading to 16-unsaturated C(19) steroid formation from pregnenolone, one of these involving 5-pregnene-3beta,20beta-diol as an intermediate. Possible mechanisms are presented and discussed.

Steroid Biosynthesis and Metabolism during Phenobarbital (PB) Block of PMS—Induced Ovulation in Immature Rats*

Abstract: Phenobarbital (PB) block of ovulation in PMS—primed (day 30) immature rats is associated with altered ovarian steroidogenesis from 144–C—cholesterol and liver metabolism of 144–C—progesterone. Ovaries from PB—treated (1:30 PM on day 32) and untreated rats were incubated with 144–C—cholesterol. The incubations with the PB—treated ovaries showed a decreased accumulation of the following steroids: 1) progesterone; 2) 20a—hydroxypregn–4–en–3–one; 3) dehydroepiandrosterone; 4) androstenedione; 5) testosterone; 6) estrone; 7) 173–estradiol; and 8') estriol and an increased accumulation of pregnenolone and 17–hydroxypregnenolone, as compared to the PB untreated controls. Liver tissue from these same rats when incubated with 144–C–progesterone showed in the PB—treated group an increased metabolism of progesterone and an increased conversion of progesterone to pregnenolone ( a reversal not previously shown in liver), as compared to rats not treated with PB. The higher hepatic conversion of progesterone was not ass...

Steroid hormones and prostaglandins.

Abstract: The structure and function of estrogens progesterone androgens and prostaglandins are described in this book chapter. Topics include the chemistry biosynthesis metabolism production and excretion biologic effects and pharmacologic uses e.g. effects on secondary sex structures and overall effects in pregnancy. The unified concept of steroid biosynthesis and metabolism presented is based on the following broad generalizations about steroids as a class of hormones: 1) steroids are ultimately derived from the simple 2-carbon substance acetate via cholesterol and pregnenolone; 2) location and types of enzymes as well as the pathways for steroid hormones are remarkably similar for each of the endocrine tissues (only the control mechanisms tropic hormones and histology may vary.); 3) steroids can also be synthesized from intermediate blood-borne precursors; and 4) metabolism of steroids after secretion occurs in many body tissues but the liver is the central location.

Steroid Biosynthesis in Vitro by Transplantable Interstitial Cell Tumor of Mice. III. Metabolism of Pregnenolone in the Cultured Tumor Cell

Abstract: A testicular interstitial cell tumor which occured spontaneously in a mouse of KF strain was found transplantable, and was able to produce corticoids as well as androgens, when incubated in vitro with steroid substrates (Endocrinology 83: 659, 196S, and 84: 123, 1969). These tumor cells were cultured in vitro in the presence of 3H-labeled pregnenolone. The substrate was transformed by the cells to progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-pregnanedione, 3α-hydroxy-5α-pregnan-20-one, 6β-hydroxyprogesterone, and 20α-hydroxypregn- 4-en-3-one, but not to any adrenal corticoid. On the other hand, when pregnenolone was incubated with the slices of the interstitial cell tumor which was immediately taken from the tumor-bearing mice, 11-deoxycorticosterone was identified as one of the major metabolites, in addition to testosterone. Due to the oxygen-limited condition of the in vitro culture, the activities of the enzymes such as Δ4-5αhydrogenase, 3α-hydroxysteroid dehydrogenase, etc....

Steroid Biosynthesis and Lymphocytotoxic Effects in Prostatic Cancer

Abstract: To the Editor.— Robinson and Thomas 1 reported on the fall of serum testosterone levels and the subjective improvement in patients with cancer of the prostate treated with a combination of diethylstilbestrol and amino-glutethimide, a powerful inhibitor of adrenal corticosteroid biosynthesis. On the basis of animal experimentation, we had suggested the use of aminoglutethimide in those patients with metastatic carcinoma of the prostate who failed to respond to conventional treatment or who suffered a relapse after an initial response. 2 Further investigation (unpublished data) seems to indicate that immunological mechanisms are involved as well: the inhibition of steroid biosynthesis, by removing the lympholytic effect of corticosteriods, produces a marked lymphoid hyperplasia and an increase in the number of circulating lymphocytes. Ablin and Baird ( 216: 2015,1971) reported the presence of lymphocytotoxic antibodies in patients with prostatic cancer. It appears, then, that inhibition of steroid biosynthesis is capable of counteracting the lymphocytotoxic effect

Steroid biosynthesis in gonadal tissue from patients with testicular feminization.

Abstract: The biosynthesis of sulfate conjugates and unconjugated steroids has been compared in two siblings aged 19 and 21, and a 52-year-old patient with the complete form of testicular feminization Incubation of homogenates of gonadal tissue with 14C-pregnenolone (P) and 3H-pregnenolone-sulfate (PS) revealed that the conversion of P to PS was 68% in the older subject, and less than 1% in the two younger subjects; and the conversion to dehydroepiandrosterone sulfate (DHAS) was 242% in the older subject, and 21 and 02% in the two younger subjects The recovery of unmetabolized PS was 419% in the older subject, and 50 and 137% in the two younger subjects The formation of testosterone from P was 42 and 22% in the two younger subjects, and 05% in the older subject, and the 3H/14C ratio indicated that the utilization of PS in testosterone biosynthesis was greater in the younger patients than in the older subject Incubation of 14C-dehydroepiandro-sterone (D) and 3H-DHAS with testicular tissue from the 21-y

Localizations and biological activities of HCG fractions in rat organs.

Abstract: This study was undertaken to determine which biological site or immunological site in the HCG molecule is essential for uptake of HCG by the ovaries. HCG was obtained from the urine of patients with trophoblastic dieseases by This study was undertaken to determine which biological site or immunological site in the HCG molecule is essential for uptake of HCG by the ovaries. HCG was obtained from the urine of patients with trophoblastic dieseases by adsorption on kaolin. This preparation gave two distinct immunological fractions on Sephadex G-100 column chromatography. One fraction (antigen-1;Ag-1) had both gonadotropic and immunological activities present in HCG, while the other (antigen 2; Ag-2) had only immunological activity of HCG. 131I Ag-1 and 125I Ag-2 were injected into rats intravenously and the localizations of 131I and 125I in each organ and their subcellular fractions were measured by the paired label technique. After injection of HCG, Ag-1 and Ag-2, the activities of Δ5-3β-hydroxysteroid dehydrogenase (3β-HSD) in the adrenals and ovaries were measured as an index of steroid biosynthesis. The results obtained were as follows:1. 131I Ag-1 was taken specifically in the ovaries and the ratio of the 131I Ag-1 to 125I Ag-2 in the microsomal fraction was 14:1, 3hours after injection of the mixture containing cold HCG. The heated 131I Ag-1, which possessed only the immunological activity of HCG was not taken specifically in ovaries. These results suggest that the biological site in HCG molecule might be essential for picking up HCG by ovaries.2. The percentage of 125I Ag-2 localization in kidney gradually increased, but no significant change was found in adrenals, thyroid, uterus, liver and blood.3. 3β-HSD activity in the ovary was stimulated by the administration of HCG and Ag-1, but slightly inhibited by Ag-2. 3β-HSD activity in the adrenals was clearly inhibited by Ag-2. These results suggest that Ag-2 possibly has some other biological activity.