Hypothalamic Cellular and Molecular Mechanisms Helping to Satisfy Axiomatic Requirements for Reproduction

In the absence of universal equations expressing neurobiological findings, the safest theoretical approach for the neuroendocrinologist is to start from axiomatic requirements for biologically adaptive neural mechanisms, in our case for reproduction. From this emerge two themes: the likely importance of interactions between internal (hormonal) and external signals in controlling gene expression relevant to reproductive functions; and, second, the vision of molecular interactions on DNA subserving environmental impacts on reproduction. The first theoretical notion has so far yielded data showing a role for synaptic inputs during the onset of estradiol actions for the hormone's induction of enkephalin mRNA, a finding which parallels earlier behavioral results. As well, noxious somatosensory inputs interact with estrogens and progesterone in their influence on enkephalin gene expression. The second theme led to novel investigations of thyroid influences on reproductive molecular biology and behavior, including the ability of exogenous or endogenous thyroid hormones to reduce female mating responses. Since elevated thyroid hormone levels could signal environmental cold, our experiments offer the possibility of explaining ethological facts at a molecular level. More generally, nuclear hormone receptor interactions on the surface of DNA may offer a new level of neural integration revealed first by hormone effects in neuroendocrine cells.     

Plasma lipid oxidation and susceptibility of low-density lipoproteins to oxidation in male patients with stable coronary artery disease

Objectives: Oxidative modifications of low-density lipoproteins (LDL) are considered to be important in the pathogenesis of atherosclerosis. However, the data on the association between LDL oxidation and severity of clinical manifestations of coronary artery disease (CAD) are contradictory. Previous reports were concerned mostly with unstable angina patients. The present study was undertaken to evaluate plasma lipid oxidation status in patients with stable CAD.

Design and Methods: 37 male patients with angiographically confirmed CAD (asymptomatic or suffering from stable angina pectoris) and 32 control subjects were used in the study. Plasma levels of vitamin E and products of lipid peroxidation, as well as parameters of the test for oxidizability of LDL in vitro were measured.

Results: We did not find differences between 2 groups of individuals regarding the levels of products of lipid peroxidation, vitamin E levels, lag time, maximal rate of oxidation, and total amount of conjugated dienes in the test for oxidizability of LDL.

Conclusion: The results of our study challenge, but do not disprove, the oxidative hypothesis of atherosclerosis. Real atherosclerotic modifications of plasma LDL occur apparently in the vascular wall after trapping of LDL by the interstitial matrix. The rise in oxidative parameters in unstable angina reported in the literature may not be the cause of the disease but, rather, the consequence of the multiple brief episodes of ischemia-reperfusion.     

不同生物素检测系统在核酸分子杂交检测中的应用——Ⅱ 碱性磷酸酶标记亲和素及胶体金标记链霉亲和素检测系统

分别应用碱性磷酸酶标记亲和素和胶体金标记链霉亲和素对斑点杂交结果进行检测。通过提高溶液中离子浓度和pH值的方法基本消除了碱性磷酸酶标记亲和素与核酸的非特异结合,这一检测系统的检测敏感性可达到1pg。胶体金标记链霉亲和素的检测效果欠佳,仅为12.5ng。     

Testosterone-induced decrement of prostatic vascular resistance in rats is reversed by estrogens

The function and growth of the rat prostate are stimulated by androgens and inhibited by estrogens. To study the influence of these hormones on the prostatic blood flow, prostatic vascular resistance was measured in castrated adult rats, which were testosterone supplemented and treated with different estrogenic substances. Prostatic blood flow was measured using the microsphere technique. Testosterone supplementation for 8-9 days after castration resulted in decreased vascular resistance in both the ventral and dorsolateral prostates. In testosterone-supplemented rats, treatment for the same period of time with estradiol benzoate, ethinyl estradiol, and diethylstilbestrol induced increased vascular resistance in both the ventral and dorsolateral prostates. However, treatment with estromustine or estramustine did not change prostatic vascular resistance significantly. It was concluded that the testosterone-induced decrease of prostatic vascular resistance was reversed by estradiol, ethinyl estradiol, and diethylstilbestrol, possibly by a direct effect on the prostate.     

Bilirubin diglucuronide as the main source for in vitro formation of delta bilirubin

To clarify which of the bilirubin moieties is responsible for the formation of bilirubin bonded to albumin (delta bilirubin) in icteric serum, the in vitro formation of delta bilirubin from bile acid-free bilirubin glucuronides and unconjugated bilirubin was examined by high-performance liquid chromatography. Bovine serum albumin (150 mumol/liter) was mixed with equimolar bilirubin diglucuronide (BDG), bilirubin monoglucuronide (BMG), or unconjugated bilirubin (UCB) and incubated in the dark at 37 degrees C under argon gas saturation. Although no delta bilirubin was formed immediately, formation eventually occurred and increased with time. A similar amount of delta bilirubin was formed when human serum albumin was used instead of bovine serum albumin. Of the three types of bilirubin, BDG was found to be the greatest source of delta bilirubin, whereas UCB produced the least. On the other hand, photoirradiation of a mixture of bovine serum albumin and UCB at a molar ratio of 1:1 resulted 6 hr later in the formation of three times as much delta bilirubin as in nonirradiated specimens. This photoinduced delta bilirubin formation increased further when the UCB/albumin molar ratio was increased to 2:1.     

Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens

Thirteen boys and 15 girls with a history of prenatal exposure to medroxyprogesterone acetate only and 22 boys and 15 girls with exposure to a variety of progestogens and estrogens singly or in combination were studied at age 8–14 years in comparison to closely pair-matched, unexposed controls. This report concerns the findings on sex-dimorphic behavior as assessed by separate interviews with the child and his/her mother. Hormone-exposed boys and controls differed little, while in girls prenatal sex hormone treatment seemed to be associated with some degree of increased stereotypic femininity.This work was supported in part by grants from the Spencer Foundation, the William T. Grant Foundation, and the Ford Foundation, and by the following grants of the United States Public Health Service: NIMH Clinical Research Center Grant MH-30906, NIMH Research Grant MH-34635, and NCI Research Grant Y01-CN-00711.     

Variations of the excretion curves of seven urinary estrogens during late pregnancy

The variations of the excretion curves of 7 different urinary estrogens have been studied by gas chromatography in 15 uncomplicated pregnancies during the last quarter or the last 2 wk before term. Normal values are indicated. When the pattern of each pregnancy is studied separately, the variations observed in estriol percentages are contrary to the variations of 16α-hydroxyestrone and of 16-oxoestradiol but the sum of these percentages is always constant in the last quarter of pregnancy. In the last days prior term, 16α-hydroxyestrone and 16-oxoestradiol are the only estrogens reaching, as a rule, two peak values.     

A multicomponent system of estradiol-binding proteins in rat liver cytosol and its dependence on sex steroids

The marked sex differences in the ratio between the hormonal capacity of estradiol-binding components with Stokes' radii (a) of 7.0 and 2.5 nm observed in sexually mature animals are somewhat reduced but do not disappear completely after gonadectomy. Prolonged administration of estradiol (50 g, 8days) to gonadectomized rats leads to depression of the estradiol-binding activity of all components of liver cytosol of females and males. Injection of testosterone propionate (2 mg, 8 days) into gonadectomized animals leads to selective stimulation of a special estrogen-binding protein with a=2.5 nm, normally characteristic of males alone, in both males and females. It is postulated that sex differences in the system of estradiol-binding proteins of the rat liver cytosol are due to sexual differentiation of the system in the early stages of development, on the one hand, and to the active regulatory influence of androgens and estrogens in the late stages of development, on the other hand.Laboratory of Endocrinology, Biological Faculty, M. V. Lomonosov Moscow State University. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 548–551, May, 1977.     

Quantitation of 5-bromo-2-deoxyuridine incorporation into DNA: an enzyme immunoassay for the assessment of the lymphoid cell proliferative response

As an alternative to the measurement of radiolabeled thymidine incorporated into DNA, a method is presented in which thymidine has been replaced by its analogue, 5-bromo-2-deoxyuridine (BUdR). BUdR incorporated into DNA (BUdR-DNA) is measured by a sandwich-type enzyme immunoassay using a monoclonal anti-BUdR antibody. This method allows the quantitation of 4 ng of BUdR-DNA. Comparative experiments with myeloma cells and LPS stimulated spleen B-cells have shown that this technique is at least as sensitive as the traditional counting of [3H]thymidine.