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Biomedical subjects

B H Shapiro

Publications and source records attributed to B H Shapiro.

At least 73 records · Page 4Linked to original sources
PubMed1985

Perinatal induction of hepatic aminopyrine N-demethylase by maternal exposure to phenytoin.

Phenytoin is one of the most commonly used anticonvulsants in pregnant epileptic women. Unrelatedly, the drug is also an inducer of hepatic drug metabolizing enzymes. We report here that maternal treatment with therapeutic-like doses for the rat of phenytoin produces significant elevations in the Michaelis constants and maximal velocities of hepatic aminopyrine N-demethylase in the dams' 8-day-old offspring. Although the drug apparently had little, if any, adverse effects on the course of pregnancy or neonatal development, it appears that the maternally administered phenytoin was transferred to the perinates where it induced hepatic drug metabolizing enzymes.

Aminopyrine N-Demethylase↗
PubMed1984

Androgenic repression of hexobarbitone metabolism and action in Crl:CD-1 (ICR)BR mice.

Mice of the Crl:CD-1 (ICR)BR strain exhibit a sexual dimorphism in hexobarbitone metabolism and action. Compared to females, males have a lower Vmax and a higher Km for hepatic microsomal hexobarbitone hydroxylase. In agreement with the enzyme studies, hexobarbitone-induced sleeping times were greater for males than for females. Results from experiments measuring hexobarbitone metabolism and action in castrate, testosterone and gonadotropin-treated mice indicate that the sexual differences in drug metabolism and action found in Crl:CD-1 (ICR)BR mice are due to the normally repressive effects of testicular androgens on the activities of the hepatic mono-oxygenases. These findings are in dramatic contrast to studies with rats where it has been shown that androgens induce mono-oxygenases. Furthermore, in the case of the mouse, changes in the activity of hexobarbitone hydroxylase in response to alterations in androgen levels require weeks, while in the rat, androgenic-induced changes are apparent within a matter of days.

Aging↗
PubMed1982

Inhibition of hepatic monooxygenases in neonatal rats by thyroxine.

The effect of thyroxine administration on the activities of hepatic microsomal monooxygenases were studied in neonatal rats. While there were no sexual differences in the activities of hepatic hexobarbital hydroxylase, cytochrome P-450 and cytochrome b5 in 8 day old rats, thyroxine administration significantly reduced the activities of these monooxygenases in both male and female neonates. The results suggest that the liver of the neonatal rat has not developed the ability to respond to the enzyme-stimulating effects of thyroxine as reported for adults.

Animals↗
PubMed1981

Sexual dimorphism and the effects of the X-linked Tfm locus on hexobarbitone metabolism and action in mice.

1 Normal males of the testicular feminized strain of mice (Tfm) had longer hexobarbitone-induced sleeping times than females, and hepatic hexobarbitone hydroxylase activity different in that the Km was higher and the Vmax lower in the male. 2 Castration and androgen replacement studies indicated that testicular androgens were responsible for the sexual differences in drug metabolism found in this mouse strain. 3 Hepatic hexobarbitone metabolism and action were feminized in the intact, androgen-insensitive, genetically male Tfm mouse. Furthermore, hexobarbitone hydroxylase activities were less responsive to large doses of testosterone in Tfm mice than in normal males. 4 The Tfm mouse with a deficiency in androgen receptors responded to the enzyme-inductive effects of phenobarbitone and softwood bedding, indicating that these inducers do not act through the androgen receptors.

Androgen-Insensitivity Syndrome↗
PubMed1980

The testicular feminized rat: a naturally occurring model of androgen independent brain masculinization.

Although genotypically male (XY), the testicular feminized rat develops as an anatomic female because of an inherited deficiency in intracellular androgen receptors that prevents androgen imprinting of sexual primordia. However, the ability of testicular feminized rats to exhibit male-like sexual behavior and little feminine sexual behavior suggests that the brain can be masculinized without androgens.

Androgen-Insensitivity Syndrome↗
PubMed1980

Phenobarbital exposure in utero: alterations in female reproductive function in rats.

Phenobarbital administration to pregnant rats from day 12 to day 19 of gestation suppressed body weight gain and produced significant effects on reproductive function in their offspring. These effects included delays in the onset of puberty, disorders in the estrous cycle, and infertility. Moreover, the animals exposed to phenobarbital in utero showed altered concentrations of sex steroids, gonadotrophic hormones, and estrogen receptors. These findings suggest that phenobarbital treatment during prenatal development can produce permanent alterations in sexual maturation.

Animals↗
PubMed1980

Reproductive dysfunction in male rats following prenatal exposure to phenobarbital.

The effect of prenatal exposure to phenobarbital (40mg/Kg/day from day 12 to day 19 of pregnancy) on sexual development of male offspring was investigated. Anogenital distance of the male offspring exposed to phenobarbital was significantly smaller. Testicular descent was delayed by 1-3 days, but the age of onset of puberty did not change. Fertility was reduced significantly (P less than .05) in phenobarbital exposed animals compared to that of control. Upon sacrifice, the weight of the seminal vesicles of treated rats was smaller compared to control, but the weight of liver was increased. Hormone measurement in adult age showed a significant reduction in both testosterone and luteinizing hormone levels in the phenobarbital exposed males. Moreover, prenatal treatment with phenobarbital produced an elevated level of cytoplasmic androgen receptor in the seminal vesicles of the adult rats. These findings suggest that phenobarbital treatment during prenatal development can produce some permanent alterations in the process of sexual maturation.

Animals↗
PubMed1976

Is feminine differentiation of the brain hormonally determined?

The androgen insensitive, genetically male rat pseudohermaphrodite displays neither masculine or feminine sexual behavior when primed with the appropriate sex hormones. Although in the absence of androgen imprinting the animal develops anatomically as female, our results suggest that feminine differentiation of the brain requires active imprinting by perinatal hormone(s), possibly adrenal progesterone.

Animals↗
PubMed1976

Effects of new multi-site hormone blockers on the fertility of male rats.

The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.

Androstanes↗
PubMed1975

Testicular maintenance and masculinized development of the vagina of the androgen-insensitive male rat pseudohermaphrodite.

The vaginae of about one-third of androgen-insensitive male rat pseudohermaphrodites never open nor can they be opened by the administration of estrogen, progesterone or andorgens. The vaginae of the remaining pseudohermaphrodites open significantly later than normal females, and, once open, require the presence of the testes or exogenous estrogen to maintain their patency. These defects in the vaginal development of the pseudohermaphrodite may be due to some perinatal masculinization of the perineum, unlike most of the phenotypically female development exhibited by this animal.

Aging↗
PubMed1975

Masculine-liky hypothalamic-pituitary axis in the androgen-insensitive genetically male rat pseudohermaphrodite.

The hypothalamic-pituitary sex of the androgen insensitive, genetically male rat pseudohermaphrodite was studied by examining its vaginal cytology, response to ovarian transplants and urinary steroidal excretion patterns. More than half the pseudohermaphrodites studied were in constant vaginal estrus, while the remaining rats displayed either persistent diestrus or irregular cyclicity tending towards lengthened estrus. Following gonadectomy and ovarian transplantation, normal females displayed regular 14-day cycles while pseudohermaphrodites remained in constant vaginal estrus. In pseudohermaphrodites with ovarian transplants, only C19 steroids were detected in the urine while females excreted both C21 and C19 steroids. Indicative of the urinary findings, transplants in females had corpora lutea and maturing follicles while grafts from pseudohermaphrodites and males contained follicular cysts and luteinized theca. In addition, distribution and activity of histochemical 3beta-hydroxy-delta5 steroid oxidoreductase were similar in the grafts from pseudohermaphrodites and males, but unlike the females. Although previous reports have shown that much of the sex-dependent differentiation of the genetic male rat pseudohermaphrodite is phenotypically female, our results suggest that the phenotype of the hypothalamic-pituitary axis of this animal is, at least in certain respects, male.

Animals↗
PubMed1975

Pituitary hormone secretion in the genectically male rat pseudohermaphrodite.

Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicated no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamic-pituitary system.

Animals↗