PubMed Health⌕ Search

Biomedical subjects

B G Steinetz

Publications and source records attributed to B G Steinetz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Serum relaxin and progesterone concentrations in pregnant, pseudopregnant, and ovariectomized, progestin-treated pregnant bitches: detection of relaxin as a marker of pregnancy.

Serum concentrations of relaxin and progesterone were measured by specific radioimmunoassays in pregnant, pseudopregnant, or ovariectomized (between gestation weeks 4 and 5) pregnant Labrador Retriever bitches. Daily administration of 17 alpha-ethyl-19-nortestosterone was performed to maintain gestation in the ovariectomized pregnant bitches. This synthetic gestagen was selected because it did not interfere with the assay for endogenously secreted progesterone concentration in serum. Serum progesterone concentration was high in ovarian-intact pregnant or pseudopregnant bitches, but the mean progesterone concentration in pseudopregnant bitches (evaluated at 4 weeks after mating) was only 56% of the concentration in pregnant bitches. After ovariectomy, serum progesterone concentration decreased to undetectable values. Unlike progesterone, serum relaxin concentration increased during the latter half of pregnancy in the ovarian-intact and in the ovariectomized pregnant bitches, but relaxin was not detectable at any time in the pseudopregnant bitches. The amount of relaxin measured in the ovariectomized pregnant bitches was less (P less than 0.05) than that in ovarian-intact bitches, suggesting that the ovaries may have contributed to the total circulating relaxin concentration in the latter. Placental production of relaxin might have accounted for the serum relaxin concentration after ovariectomy; thus, the ovary and placenta each may secrete relaxin during gestation in bitches. Regardless of its source, measurement of serum relaxin concentration may offer a useful way of distinction between pregnancy and pseudopregnancy in dogs.

Animals↗
PubMed1988

Structure of a porcine relaxin inactive on the mouse pubic ligament.

In addition to B31 (CM-a) and B28 (CM-B) relaxins, acid-acetone extracts of ovaries of pregnant sows contain a third major relaxin species (relaxin C). The major components of relaxin C possess about half the activity of CM-a or CM-B in the guinea pig palpation assay, but are completely inactive in the mouse pubic ligament assay. Its uterotrophic and protein anabolic effects in ovariectomized, estrogen-primed mice, however, are comparable to those of CM-B. Sequence analysis indicates that the two major components of relaxin C, like the other porcine relaxins, consist of two polypeptide chains linked by disulfide bonds. The shorter (A) chains are identical to the A chains of the other porcine relaxins, except for the absence of the N-terminal arginine residue. The B chains display microheterogeneity; the B sequences of the two predominant species are the same as those of the other porcine relaxins through B25, but terminate at valine residue B25 or serine residue B26, respectively.

Amino Acid Sequence↗
PubMed1988

The source of relaxin in pregnant Syrian hamsters.

Serum immunoreactive relaxin (IR) was measured on days 8, 10, and 14 of gestation in intact and ovariectomized (day 8 of pregnancy) hamsters. In intact hamsters, IR increased from 3-4 ng/ml on day 8 to 20 ng/ml by day 14 of pregnancy. After ovariectomy on day 8, pregnancy failed, and IR decreased rapidly to 0.29 ng/ml on day 14. However, when pregnancy was maintained in ovariectomized hamsters by daily injections of 0.1 microgram 17 beta-estradiol and 4 mg progesterone, serum IR rose to levels similar to those in intact hamsters on days 10 and 14 of pregnancy (i.e. 15 and 20 ng/ml, respectively). Placentas were obtained from other groups of hamsters on days 11, 14, and 15 of pregnancy and homogenized for bioassay by the classical guinea pig pubic symphysis palpation bioassay. Homogenates of placentas obtained on days 14 and 15 contained, respectively, 4 and 10 micrograms eq porcine relaxin/serum relaxin/g fresh tissue. The placenta, rather than the ovary, appears to be the source of during pregnancy in the hamster.

Animals↗
PubMed1987

Plasma relaxin levels in pregnant and lactating dogs.

The pattern of plasma relaxin has been studied during pregnancy and following parturition in two breeds of dogs, Labrador retrievers and beagle hounds. Blood samples were collected at weekly intervals following mating and during pregnancy, parturition, and lactation. Relaxin, progesterone, and estradiol-17 beta were determined by specific double antibody radioimmunoassays. Immunoreactive relaxin (IR) was not detectable in plasma of male dogs, bitches in anestrous, or pseudopregnant bitches that had undergone an infertile mating. IR was first detectable in plasma in the third or fourth week of gestation in retrievers and beagles. IR levels rose to a peak of 4-5 ng/ml in both breeds. The peak plasma levels were reached 2-3 wk before whelping and declined significantly prior to that event. IR then persisted during lactation at a level of 0.5-2 ng/ml for 4-9 wk, but was significantly higher (p less than 0.01) at all time periods and persisted longer in labradors than in beagles. The secretion of relaxin did not parallel that of progesterone, which was highly elevated in the first samples drawn (during the first week of pregnancy), remained high through 5 or 6 wk of gestation, then slowly declined until the time of parturition, becoming undetectable during lactation. Plasma estradiol-17 beta was low after the second week of pregnancy in both breeds of dogs and became undetectable during lactation. The source of relaxin in the dog is not known currently, and its sites of secretion and role in pregnancy are currently under investigation in our laboratories. The dog is the first species in which plasma IR is detectable during lactation using antibody R6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Isolation, purification, and the sequence of relaxin from spiny dogfish (Squalus acanthias).

A relaxin-like molecule has been isolated from the ovaries of the spiny dogfish (Squalus acanthias) which consists, like porcine relaxin, of two chains linked by the insulin-type disulfide bonds. The total number of amino acids is 54 of which 24 are in the A chain and 30 in the B chain. The molecular masses, calculated from the amino acid compositions, are 2510 Da for the A chain and 3370 Da for the B chain, making a total of 5880 Da. The N-terminus of the B chain is protected by a 5-oxoproline (pyrrolidone carboxylic acid) residue which is also found in the same position in the relaxins of sand tiger shark, pig, and man, whereas the relaxin of the rat has its 5-oxoproline residue at the N-terminal of the A chain. By all available criteria, S. acanthias relaxin is a typical member of the relaxin family although the sequence homology to mammalian relaxins is limited to about 45% of its amino acid residues. In contrast, the dogfish relaxin shows about 80% homology with sand tiger shark relaxin (the first such interspecies similarity to be observed) and has about twice the biological activity (mouse pubic symphysis test) when compared to sand tiger relaxin.

Amino Acid Sequence↗
PubMed1985

Effects of altered endocrine function on biliary metabolites of [4-14C]androst-4-ene-3,17-dione in rats. Possible utility as a model for identifying anti-atherosclerotic agents.

Atherosclerosis, coronary artery disease and elevated serum cholesterol are frequently associated with an abnormal pattern of androgen metabolites, especially an elevation of etiocholanolone (E) and/or epiandrosterone (EA) relative to androsterone (A). Therapeutic correction of these metabolic defects may lower serum cholesterol. We have attempted to reproduce this metabolic syndrome in rats by altering their endocrine status. Intact male rats excreted very little A or E in their bile; more than 80% of the [4-14C]A-dione was excreted as unknown polar compounds. Adrenalectomy, thyroidectomy or streptozotocin diabetes induced little or no change in the excretion of both E and A and did not alter the A/E ratio. Hypophysectomy (hypox), however, resulted in a huge increase in E excretion and a 10-fold decrease in the A/E ratio. Treatment of hypophysectomized males with bovine growth hormone (bGH) but not testosterone or thyroxine restored the pattern of androgen metabolites to that of intact male rats. Intact female rats excreted mainly A, and this was decreased by ovariectomy. Hypophysectomy, however, resulted in a marked increase in E and a corresponding large decrease in A excretion. Treatment of hypox females with estradiol or triiodothyronine did not correct the metabolic defects in A and E production, whereas GH resulted in a pattern of A-dione metabolism resembling that of intact males; i.e., primarily polar metabolites with low A and E. Hypophysectomy thus results in a dramatic increase in 5 beta-reductase activity in male and female rats. GH therapy restores the metabolic pathway to that seen in intact males. Our objective had been to find a model capable of detecting substances which would increase A and decrease E production. The male rat (regardless of endocrine status) has little 5 alpha-reductase activity. The intact female rat, however, has high 5 alpha-reductase activity, and retains significant 5 alpha-reductase in the absence of the ovaries. In hypox females, 5 alpha-reductase was much reduced while 5 beta-reductase was increased. Furthermore, serum cholesterol was elevated in hypox females but could be lowered by exogenous androsterone. Thus the hypox female rat appears to offer the best model for identifying non-hormonal agents which could enhance the production of A and/or decrease the production of E. Such agents might favorably influence cholesterol metabolism.

Androstenedione↗
PubMed1985

Identification of potential antiatherosclerotic/hypolipidemic agents by their effect on hepatic conversion of androst-4-ene-3,17-dione to etiocholanolone and androsterone.

Clinical observations have shown that hypercholesterolemia is associated with abnormal androgen metabolism, viz. an increased excretion of etiocholanolone (E) relative to androsterone (A). Substances which restore the A/E ratio to normal likewise lower serum cholesterol. Postulating that the abnormal steroid and sterol metabolism may be either causally related or dependent on the same metabolic defect, we have developed in vitro and in vivo models to select drugs which favorably effect the ratio of A to E produced from [4-14C]androst-4-ene-3,17-dione [4-14C]A-dione). The in vitro model employs a mixture of rat liver microsomal delta 4-3-ketosteroid-5 alpha-reductase and cytosolic 3 alpha-hydroxysteroid dehydrogenase and delta 4-3-ketosteroid-5 beta-reductase. Kinetic and mechanistic studies have been performed on active compounds using this in vitro assay. The in vivo model employs i.v. injection of [4-14C]A-dione followed by collection of bile in anesthetized, hypophysectomized female rats. Many compounds preselected in the in vitro assay likewise reduced the A/E ratio in vivo. One of these compounds (CGS 10614A) also lowered serum cholesterol and reduced the incidence and severity of atherosclerotic lesions in aortas of cholesterol-fed rabbits.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Effects of aminoglutethimide on cervical dilatability and serum immunoreactive relaxin in pregnant rats.

Administration of aminoglutethimide (AG) at a daily sc dose of 20 mg/kg to rats from the 10th to 20th days of pregnancy resulted in fetal wastage, increased placental weights, and decreased placental alkaline phosphatase. In an effort to determine the endocrine problems relating to these abnormalities, serum relaxin (R) and progesterone (P) levels were determined by RIA and cervical distensibility was measured: All three parameters were subnormal in AG-treated rats. Therapy with estrogen (E) or (P) failed to correct any of the physiological problems associated with AG treatment, but a combination of these steroids increased fetal survival to control levels. However, cervical dilation in preparation for parturition failed to occur. Relaxin therapy alone increased cervical dilation but did not enhance fetal survival. A combination of E, P, and R maintained a normal complement of fetuses and provided normal cervical dilation. None of the treatments prevented placental enlargement but P treatment tended to maintain normal placental alkaline phosphatase.

Aminoglutethimide↗
PubMed1984

Relaxin in human decidua and term placenta.

Using both a homologous porcine RIA and 3 bioassays, we investigated the relaxin content of human decidua from first trimester and term gestations and of placentas at term. Aqueous extracts of these tissues yielded only between 211 and 1090 pg immunoreactive relaxin/g fresh tissue. Neither acetonehexane extraction, octadecylsilica cartridge elution nor molecular sieve chromatography increased these relaxin levels. Compared with term decidua, first trimester decidua contained significantly higher levels of immunoreactive relaxin. In vitro studies did not evidence significant relaxin production by either decidual or placental tissues, even in the presence of decidual prolactin production. These results are in direct contrast to earlier reports of high concentrations of relaxin in decidua and placenta.

Animals↗
PubMed1983

The effect of relaxin and progesterone on rat uterine contractions.

The effect of porcine relaxin on electrically stimulated in vitro contractions of isolated uterine horn segments from estrogen-pretreated immature rats was studied. Relaxin decreased the amplitude of contractions. A mean of 8.3 ng/ml of relaxin produced a 90% decrease in contraction amplitude. There was a minimal effect of 1.0 microgram/ml of progesterone on contraction amplitude. In vitro pretreatment of the isolated uterine segment with this dose of progesterone for 15 minutes did not significantly affect the dose of relaxin needed to decrease the amplitude of contractions. In contrast, pretreatment with progesterone for 45 minutes significantly decreased the concentration of relaxin needed to decrease contraction amplitude. Only 4.7 ng/ml of relaxin was needed to produce a 90% decrease in amplitude after progesterone pretreatment for 45 minutes (p less than 0.005). Relaxin and progesterone synergize in decreasing the amplitude of uterine contractions in vitro. A similar effect may occur in vivo.

Animals↗
PubMed1983

Effect of anti-relaxin antiserum on sperm motility in vitro.

Rabbit anti-relaxin antisera, but not normal rabbit sera, causes a rapid decline of motility of washed human sperm. Preincubation of the antisera with relaxin eliminates this effect. This sperm immobilization effect can serve as a basis of a rapid screening test for anti-relaxin antisera and as a novel adjuvant to barrier contraceptive methods.

Antigen-Antibody Complex↗
PubMed1982

Synergistic effect of human relaxin and progesterone on human myometrial contractions.

In an in vitro human myometrial strip system, both relaxin and progesterone can independently decrease the amplitude of spontaneous myometrial contractions. However, progesterone and relaxin synergize in this action. Doses of relaxin and progesterone which independently are ineffective, together inhibit myometrial contraction amplitude. Relaxin and progesterone are both products of the corpus luteum, a structure necessary for early pregnancy maintenance. The synergistic action of relaxin and progesterone in vitro suggests a similar in vivo physiologic effect in establishing uterine quiescence.

Adult↗