Effect of heterosexual olfactory and visual stimulation on 5-en-3 beta-hydroxysteroids and progesterone in the male rat brain

Pregnenolone, dehydroepiandrosterone and progesterone were measured in specific areas of the brain and in the retina of young adult male rats exposed to the scent or to the scent and view of young cycling females and compared to the levels obtained in males similarly exposed to other males (control). All the steroid values observed were much higher than those found in plasma, varied considerably from one area to another and responded sometimes in opposite directions to stimulation of young adult males by the scent or by the scent and view of cycling females. In male rats exposed to the scent of young cycling females pregnenolone decreased significantly only in the olfactory bulb in comparison with the controls. There were no significant changes in dehydroepiandrosterone or progesterone in this case. When male rats were exposed to the scent and view of female rats, pregnenolone again decreased significantly in the olfactory bulb while dehydroepiandrosterone increased significantly in the olfactory bulb and the retina and progesterone decreased significantly in the hypothalamus, amygdala and parietal cortex. These results are discussed in relation with a possible new role for certain steroids in neuroregulatory mechanisms related to behaviour.     

Progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone concentrations in specific regions of the human brain

The concentrations of progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone were determined in tissue samples from the human hypothalamus, anterior pituitary, pineal, amygdala and parietal cortex, taken at autopsy from male (n = 4) and female cadavers (n = 4) of various ages. The measurements were performed using radioimmunoassays for the individual steroids after the chromatographic purification of solvent extracts of tissue samples on Lipidex-5000TM. Preliminary qualitative analyses of the chromatographic profiles of various steroids by radioimmunoassay demonstrated the presence of these steroids in various regions of the brain, but an immunoreactive peak corresponding to 17-hydroxyprogesterone was not found. The concentrations (ng/g tissue wet wt.) of all steroids measured were either very low or below the limit of detection in brain tissues taken from male and female infants. In the adult brain, there was no difference in the distribution of steroids between the various regions studied. There was no sex difference in the brain tissue steroid concentrations, with the exception of testosterone which was clearly much higher in brain tissues from men as compared to women. Although testosterone was undetectable in most samples taken from adult women. 5 alpha-dihydrotestosterone could be measured in almost all samples, which suggests that this is the most important androgen in the human brain. When brain tissue steroid levels are compared with serum concentrations, it can be postulated that a state of equilibrium exists between the fraction of serum steroids which are not bound to high-affinity binding proteins and the amount of steroids in brain tissues.     

Sex steroids in the serum of Caspian sturgeons and their specific cytosol binding in brain and gonads during the migratory cycle

Testosterone (T) and estradiol 17β (E2) concentrations were measured in the serum of Russian, stellate and beluga sturgeons. Hormone concentrations were comparatively low during the feeding period at sea and did not differ between seasons or species. At the beginning of the spring spawning migration into freshwater, both of the spring and winter races of Russian sturgeon ( Acipenser gueldenstaedtii ) and beluga sturgeon ( Huso huso ), as well as the spring-summer race of stellate sturgeon ( Acipenser stellatus ), exhibited a marked elevation of serum T, despite differences in their degrees of gonadal development. There were no differences in specific cytosol binding of androgens and estrogens in the forebrain of either migratory form of Russian sturgeon, while the specific binding of sex steroids was higher in the hypothalamus of the spring form. The data indicate that T and its receptors may control aspects of anadromous migration in sturgeons.     

Sex steroids and their receptors: molecular actions on brain cells

Sex steroids exert actions of paramount importance on brain cells. They contribute to shape the central nervous system during embryo development. They modulate the formation and the turnover of the interconnections between neurons. They control the function of glial cells. And they do it through a signaling machinery that is apparently simple, but that hides a level of complexity that has been unveiled only in part. Different receptor isoforms, different interactions between receptors and co-regulators, chains of events originating at the cell membrane and leading to effects in the nucleus (or the other way around) all interact to determine selective modulations of brain cells. All these actions end up in phenomenal effects on brain function that change through adolescence, pregnancy, adulthood, up to menopause and ageing. Many of these actions are relevant for degenerative processes and research may offer soon new strategies to counteract these diseases.     

Evidence for the presence of 7-hydroperoxycholest-5-en-3 beta-ol in oxidized human LDL.

Low density lipoprotein (LDL) cholesterol is known to be oxidized both in vitro and in vivo giving rise to oxygenated sterols. Conflicting results, however, have been reported concerning both the nature and the relative concentrations of these compounds in oxidized human LDL. We examined the extracts obtained from Cu(2+)-oxidized LDL. Thin layer chromatography analysis showed that the sterol mixture became more complex with reaction time. Analysis of the components by thin layer chromatography and mass spectrometry allowed to establish that 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha OOH and beta OOH) are largely prevalent among the oxysterols at early times of oxidation. These hydroperoxy derivatives have not been previously identified in oxidized LDL. The concentration of 7-hydroperoxycholest-5-en-3 beta-ol decreased with oxidation time with a concomitant increase of cholest-5-en-3 beta, 7 alpha-diol (7 alpha OH), cholest-5-en-3 beta, 7 beta-diol (7 beta OH), cholesta-3,5-dien-7-one (CD) and cholest-5-en-3 beta-ol-7-one (7CO). After 24 h of oxidation a minor component of the LDL sterols was cholestan-3 beta-ol-5,6-oxide (EP).     

Age-related changes of elements with their relationships in human cranial and spinal nerves

To elucidate compositional changes of peripheral nerves with aging, the authors investigated age-related changes of elements and their relationships in the optic, trigeminal, vagus, median, radial, ulnar, femoral, sciatic, tibial, and common peroneal nerves by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 10 men and 12 women, ranging in age from 65 to 91 yr. It was found that although accumulations of Ca and P occurred only in the trigeminal nerve at old age, it hardly occurred in the optic, vagus, median, radial, ulnar, femoral, sciatic, tibial, and common peroneal nerves at old age. The average contents of Ca and P were three and two times higher in the trigeminal nerve than in the other nine kinds of nerve, respectively. Likewise, the average content of Mg was a little higher in the trigeminal nerve compared with the other nerves. With regard to the relationships among elements, significant direct correlations were found among the contents of Ca, P, S, and Mg in most, but not all, 10 kinds of nerve. In the trigeminal nerve, a significant inverse correlation was found between the contents of S and the other elements, such as Ca, P, and Mg. Regarding the relationships between the contents of S and other elements, the nerves, except for the trigeminal nerve, differed from those found in the arteries previously reported.     

Detection of specific protein bands with melatonin-like immunoreactivity in different cell lines and human brain regions

The pineal hormone melatonin regulates various neural and endocrine processes involved in mammalian circadian rhythms. To understand how melatonin mediates these functions, we investigated melatonin-like immunoreactivity (MLI) in cell extracts and human brain. In Western immunoblots, we detected high-molecular-mass protein bands (85-135 kDa) that specifically reacted with the anti-melatonin antibody. The specific protein bands were present in cell extracts from the human brain and cell lines of different origins. The immunoreactive signal of the 135-kDa protein band was highest in a neuroendocrine PC12 cell line, which was 10-fold higher than the signal observed in any cell extracts used. The commercial antibody employed in the Western blots was further purified against serum proteins and thyroglobulins. We have previously reported that the antibody against melatonin recognizes MLI as detected by a sensitive RIA. In the present report we have detected the putative melatonin-specific binding proteins, which could contribute to the MLI. Our results suggest that melatonin binds with specific proteins in different cellular and brain extracts, the protein(s) being maximally synthesized in PC12 cells. These results may indicate a group of yet unknown proteins sharing a melatonin-like epitope or the presence of melatonin-binding protein(s) that regulate availability of free melatonin, or both.     

Sex differences in oxytocin receptor binding in forebrain regions: Correlations with social interest in brain region- and sex- specific ways

Social interest reflects the motivation to approach a conspecific for the assessment of social cues and is measured in rats by the amount of time spent investigating conspecifics. Virgin female rats show lower social interest towards unfamiliar juvenile conspecifics than virgin male rats. We hypothesized that the neuropeptide oxytocin (OT) may modulate sex differences in social interest because of the involvement of OT in pro-social behaviors. We determined whether there are sex differences in OT system parameters in the brain and whether these parameters would correlate with social interest. We also determined whether estrus phase or maternal experience would alter low social interest and whether this would correlate with changes in OT system parameters. Our results show that regardless of estrus phase, females have significantly lower OT receptor (OTR) binding densities than males in the majority of forebrain regions analyzed, including the nucleus accumbens, caudate putamen, lateral septum, bed nucleus of the stria terminalis, medial amygdala, and ventromedial hypothalamus. Interestingly, male social interest correlated positively with OTR binding densities in the medial amygdala, while female social interest correlated negatively with OTR binding densities in the central amygdala. Proestrus/estrus females showed similar social interest to non-estrus females despite increased OTR binding densities in several forebrain areas. Maternal experience had no immediate or long-lasting effects on social interest or OT brain parameters except for higher OTR binding in the medial amygdala in primiparous females. Together, these findings demonstrate that there are robust sex differences in OTR binding densities in multiple forebrain regions of rats and that OTR binding densities correlate with social interest in brain region- and sex-specific ways.     

Hydroboration of 5 alpha-ergost-8-en-3 beta-ol

Hydration via hydroboration of 5 alpha-ergost-8-en-3 beta-ol affords 5 alpha-ergostane-3 beta, 15 alpha-diol, 5 alpha, 14 beta-ergostane-3 beta, 15 beta-diol, and 5 alpha-ergostane-3 beta, 7 beta-diol, and not 5 alpha, 9 beta-ergostane-3 beta, 7 beta-diol, as previously reported by others.     

Circadian course of delta 5,3 beta-hydroxysteroids and glucocorticosteroids in the plasma and brain of rats

Corticosterone (B), pregnenolone (P) and dehydroepiandrosterone (D) undergo circadian variations in the rat plasma and brain. When the data are interpreted by the Cosinor method, the acrophases of P in brain and of D in plasma significantly precede the acrophase of B. The asynchrony of delta 5-3 beta-hydroxysteroid and glucocorticosteroid rhythms brings an additional argument in favor of separate regulatory mechanisms.     

Effects of 5alpha-androst-16-en-3alpha-ol on the pulsatile secretion of luteinizing hormone in human females

We examined the effects of 5alpha-androst-16-en-3alpha-ol (3alpha-androstenol) on pulsatile luteinizing hormone (LH) secretion in human females. The frequency of the LH pulse in the follicular phase was decreased by exposing the women to 3alpha-androstenol.     

A specific brain tract guides follower growth cones in two regions of the zebrafish brain

Neurons of the nucleus of the posterior commissure (nuc PC), an identifiable cluster of neurons in the embryonic zebrafish brain, project growth cones ventrally along the posterior commissure to the anterior tegmentum where the PC intersects two longitudinal tracts, the tract of the postoptic commissure (TPOC) and the medial longitudinal fasciculus (MLF). Once at the intersection, nuc PC growth cones turn posteriorly onto the TPOC in the dorsal tegmentum and follow it to the hindbrain. Previously we showed that in the absence of the TPOC, nuc PC growth cones often extended along aberrant path ways suggesting that fasciculation, that is, contact with TPOC axons is an important factor in guiding growth cones along their normal pathway. However, a significant number of nuc PC growth cones also followed their normal pathway suggesting that cues associated with the dorsolateral tegmentum, independent of the TPOC, can also guide nuc PC growth cones. We have now confirmed using electron microscopy that nuc PC growth cones fasciculate with axons in the TPOC. In the absence of the TPOC, the nuc PC growth cones that extend along their normal pathway do so in contact with dorsolateral neuroepithelial cells. This suggests that cues associated with these cells can also guide the nuc PC growth cones. Furthermore, in the absence of the TPOC axons, these growth cones now inappropriately turn onto axons that normally intersect the TPOC near the border of the midbrain and hindbrain, that is, at a second intersection of tracts. This suggests that fasciculation with TPOC axons may also guide nuc PC growth cones in this second region of the brain. © 1992 John Wiley & Sons, Inc.     

Iodine levels in different regions of the human brain

BackgroundIodine is a key component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), which are crucial for proper growth and development of the human body. In particular, a great body of literature has been published on the link between thyroid hormones and brain development and functioning. However, there is a lack of knowledge on the iodine levels in the human brain. The aim of this work was to determine the brain iodine levels and to contribute to the establishment of “reference” levels for iodine in the different anatomical and functional regions of normal (i.e., subjects without neurological or psychiatric diseases) human brain.MethodsThe iodine levels were determined in 14 brain regions of 52 dead subjects without evidence of neurological or psychiatric disease (n = 728 samples). Iodine was extracted from brain samples using a standard procedure and determined by inductively coupled plasma – mass spectrometry (ICP-MS).ResultsFour subjects presented abnormally high brain iodine levels (26.0 ± 14.2 μg/g) and were excluded from the overall data analysis. The average brain iodine levels for the remaining 48 subjects was 0.14 ± 0.13 μg/g dry weight. Iodine showed very heterogeneous distribution across the different brain regions, with the frontal cortex, caudate nucleus and putamen showing the highest levels. Interestingly, these brain regions are closely related to cognitive function. Iodine levels also showed a tendency to increase with age. The high levels observed in four subjects seemed to be related to previous exposure to iodine-based contrast agents widely used in radiology and computed tomography exams.ConclusionsThis paper provides important data on iodine levels at different brain regions in “normal” people, which can be used to interpret eventual imbalances in subjects with mental disorders and neurodegenerative diseases.