Drugs in the brain--cellular imaging with receptor microscopic autoradiography

For cell and tissue localization of drugs, receptor microscopic autoradiography is reviewed, including its development history, multiple testing, extensive applications and significant discoveries. This sensitive high-resolution imaging method is based on the use of radiolabeled compounds (esp. tagged with ³H or ¹²⁵I), preservation through freezing of in vivo localization of tissue constituents, cutting thin frozen sections, and close contact with the recording nuclear emulsion. After extensive testing of the utility of this method, the distribution of radiolabeled compounds has been identified and characterized for estradiol, progestagens, adrenal steroids, thyroid hormone, ecdysteroids, vitamin D, retinoic acid, metabolic indicators glucose and 2-deoxyglucose, as well as extracellular space indicators. Target cells and associated tissues have been characterized with special stains, fluorescing compounds, or combined autoradiography-immunocytochemistry with antibodies to dopamine-beta-hydroxylase, GABA, enkephalin, specific receptor proteins, or other cellular products. Blood-brain barrier and brain entries via capillary endothelium, ependyma, or circumventricular recess organs have been visualized for ³H-dexamethasone, ²¹⁰Pb lead, and ³H-1,25(OH)₂ vitamin D₃. With this histopharmacologic approach, cellular details and tissue integrative overviews can be assessed in the same preparation. As a result, information has been gained that would have been difficult or impossible otherwise. Maps of brain drug distribution have been developed and relevant target circuits have been recognized. Examples include the stria terminalis that links septal-amygdaloid-thalamic-hypothalamic structures and telencephalic limbic system components which extend as the periventricular autonomic-neuroendocrine ABC (Allocortex-Brainstem-Circuitry) system into the mid- and hindbrain. Discoveries with radiolabeled substances challenged existing paradigms, engendering new concepts and providing seminal incentives for further research toward understanding drug actions. Most notable are discoveries made during the 1980s with vitamin D in the brain together with over 50 target tissues that challenged the century-old doctrine of vitamin D's main role as ‘the calcitropic hormone’, when the new data made it apparent that the main biological function of this multifunctional sunshine hormone rather is maintenance of life and adapting vital functions to the solar environment. In the brain, vitamin D, in close relation to sex and adrenal steroids, participates in the regulation of the secretion of neuro-endocrines, such as, serotonin, dopamine, nerve growth factor, acetyl choline, with importance in prophylaxis and therapy of neuro-psychiatric disorders. Histochemical imaging with high cellular-subcellular resolution is necessary for obtaining detailed information, as this review indicates. New spectrometric methods, like MALDI-MSI, are unlikely to furnish the same information as receptor microautoradiography does, but can provide important correlative molecular information.     

Characterization of the estrous cycle and reproductive traits of the aoudad (Ammotragus lervia) in captivity

In this study the estrous cycle of the aoudad has been analyzed and characterized for the first time, using non-invasive methods for tracking reproductive cyclicity. The duration of the estrous cycle is 23 days (range 16-32 days), with a luteal phase of 17 days (range 12-27 days) and an interluteal phase of 6 days (range 3-14 days). The estrous cycle did not differ between females, but it was affected by the time of the year. Intraindividual variation of the cycle was observed in one out of the nine individuals. The average hormone concentration values, the estrogen:progestogen ratio, as well as their minimum and maximum values for each interluteal and luteal phases of the estrous cycle, are shown. Interindividual differences found in these values were basically associated with age. Females tended to start their cycle when in the presence of an adult male. Anestrus was observed in study females except for the oldest (14 years old). Age and anestrus onset were correlated, with younger females starting earlier than the older ones. This study reveals that Ammotragus reproductive biology is more similar to that of Capra than Ovis, except for some endocrinological features.     

Recent Updates on Corals from Nephtheidae

Marine natural products display a wide range of biological activities, which play a vital role in the innovation of lead compounds for the drug development. Soft corals have been ranked at the top in regard to the discovery of bioactive metabolites with potential pharmaceutical applications. Many of the isolated cembranoids revealed diverse biological activities, such as anticancer, antidiabetic and anti‐osteoporosis. Likewise, sterols from soft corals exhibited interesting biological potential as anti‐inflammatory, antituberculosis and anticancer. Consequently, investigating marine soft corals will definitely lead to the discovery of a large number of chemically varied secondary metabolites with countless bioactivities for possible applications in medicine and pharmaceutical industry. This review provides a complete survey of all metabolites isolated from the family Nephtheidae, from 2011 until November 2018, along with their natural sources and biological potential whenever possible.     

Cortisol response and ovarian hormones in juvenile and cycling female Cebus monkeys: effect of stress and dexamethasone

We examined cortisol profiles in relation to ovarian hormones and their response to a repeated composite stressor with and without dexamethasone suppression. To evaluate the day-to-day changes in circulating cortisol relative to ovarian hormones, we subjected five adult female Cebus apella monkeys daily to restraint, sedation, transport to a neighboring room for femoral venipuncture, and return to the cage throughout the menstrual cycle. The cortisol response to the repeated stressor for blood collection, its relationship with the ovarian function, and the effects of dexamethasone were evaluated in six juveniles (18-24 months old) and five adult females in the luteal phase. Blood was sampled at time 0; then the monkeys received the vehicle and their blood was sampled again at 1, 2, 4, and 24 hr. This experiment was repeated 3 weeks later, with dexamethasone (i.m. 2 mg/Kg) injected instead of vehicle. Plasma aliquots were assayed for cortisol, progesterone, and estradiol. The results revealed that from middle infancy and throughout adulthood, hypercortisolism is the norm in female Cebus monkeys. The high cortisol values remained unchanged across the cycle despite the cyclic changes in estradiol and progesterone levels. Juvenile monkeys exhibited a higher cortisol response to stress than adults, and both juvenile and adult monkeys exhibited the typical suppression by dexamethasone. A rapid suppression of progesterone co-occurred in parallel with cortisol after dexamethasone injection in juvenile monkeys, suggesting that most circulating progesterone originates in the adrenals. In contrast, adult females exhibited an overincrement of progesterone levels, in parallel with a rise in cortisol, in response to the stressor, and this effect was exacerbated by dexamethasone. The findings suggest that hypercortisolism is insufficient to disrupt ovarian development toward a normal cyclical function, and that ovarian steroids have no influence on day-to-day circulating cortisol levels. On the other hand, the overincrement of progesterone levels induced by stress and/or glucocorticoids during the early luteal phase is unlikely to interfere with the development of this phase and implantation in this monkey species.     

木奶果茎叶的化学成分研究

采用常压柱色谱和重结晶相结合的分离方法,从木奶果的茎叶提取物的乙酸乙酯部分中分离得到8个化合物,通过波谱方法及与已知样品对照的手段鉴定它们为(2S,3S,4R)-2-[(2R)-2-hydroxytetracosanoyl-amino]-1,3,4-octadecanetriol(1),Aralia cerebroside(2),(24S)-24-ethylcholesta-3β,5α,6β-triol(3),Stigmast-4-en-6β-ol-3-one(4),7-oxo-β-sitosterol(5),7α-methoxy-sigmast-5-en-3β-ol(6),β-sitosterol(7),daucosterol(8)。化合物1-6为首次从该种植物中发现的。     

Bidirectional sex-change behavior and physiological aspects in the Gorgeous goby Lythrypnus pulchellus (Gobiidae)

The Gorgeous goby Lythrypnus pulchellus shows extreme sexual plasticity with the bidirectional sex-change ability socially controlled in adults. Therefore, this study describes how the hierarchical status affects hormone synthesis through newborn hormone waste products in water and tests the influence of body size and social dominance establishment in sex reversal duration and direction. The associated changes in behavior and hormone levels are described under laboratory conditions in male–male and female–female pairs of similar and different body sizes, recording the changes until spawning. The status establishment occurred in a relatively shorter time period in male and female pairs of different sizes (1–3 days) compared to those of similar size (3–5 days), but the earlier one did not significantly affect the overall time of sex change (verified by pair spawning). The changes in gonads, hormones, and papilla occurred in sex-changer individuals, but the first one was observed in behavior. Courtship started at 3–5 days in male pairs and from 2 h to 1 day in female pairs of both groups of different and similar sizes. Hormones did not gradually move in the new sexual phenotype direction during the sex-change time course. Nonetheless, estradiol regulated sex change and 11-ketotestosterone enabled bidirectional sex change and was modulated by agonistic interactions. Cortisol is associated with status and gonadal sex change. In general, similar mechanisms underlie sex change in both directions with a temporal change sequence in phases. These results shed new light on sex-change mechanisms. Further studies should be performed to determine whether these localized changes exist in the steroid hormone synthesis along the brain–pituitary gonad axis during social and bidirectional sex changes in L. pulchellus.     

Binding Domain‐Driven Intracellular Trafficking of Sterols for Synthesis of Steroid Hormones,Bile Acids and Oxysterols

Steroid hormones, bioactive oxysterols and bile acids are all derived from the biological metabolism of lipid cholesterol. The enzymatic pathways generating these compounds have been an area of intense research for almost a century, as cholesterol and its metabolites have substantial impacts on human health. Owing to its high degree of hydrophobicity and the chemical properties that it confers to biological membranes, the distribution of cholesterol in cells is tightly controlled, with subcellular organelles exhibiting highly divergent levels of cholesterol. The manners in which cells maintain such sterol distributions are of great interest in the study of steroid and bile acid synthesis, as limiting cholesterol substrate to the enzymatic pathways is the principal mechanism by which production of steroids and bile acids is regulated. The mechanisms by which cholesterol moves within cells, however, remain poorly understood. In this review, we examine the subcellular machinery involved in cholesterol metabolism to steroid hormones and bile acid, relating it to both lipid‐ and protein‐based mechanisms facilitating intracellular and intraorganellar cholesterol movement and delivery to these pathways. In particular, we examine evidence for the involvement of specific protein domains involved in cholesterol binding, which impact cholesterol movement and metabolism in steroidogenesis and bile acid synthesis. A better understanding of the physical mechanisms by which these protein‐ and lipid‐based systems function is of fundamental importance to understanding physiological homeostasis and its perturbation.      

Role of ovarian secretions in mammary gland development and function in ruminants

The mammary gland is a dynamic organ that undergoes cyclic developmental and regressive changes during the lifetime of a female mammal. Mammogenesis begins during embryonic life with the development of the first mammary gland rudiments and ductal system. After birth, during the pre-pubertal period, the ductal growth of the mammary parenchyma occurs through the fat pad. In most of the ruminant species allometric mammary parenchyma development begins with the onset of cyclic ovarian secretions activity. The two main hormones secreted during an ovarian cycle are estradiol and progesterone. These steroid hormones are derived from cholesterol and are synthesized by theca and granulosa cells in ovaries. During puberty, the mammary parenchyma develops in a compact, highly arborescent parenchymal mass surrounded by a dense connective matrix. Ductal elongation and lobulo-alveolar development are accomplished during growth and pregnancy to prepare for future milk production. At the end of lactation, the mammary gland undergoes involution, which corresponds to a regression of the secretory tissue, a reduction in the alveolar size and a loss of mammary epithelial cells (MECs). Ovarian steroids (estradiol and progesterone) appear to be key regulators of the different stages of mammogenesis and mammary function. Through this review, the role and the importance of ovarian steroids on mammary gland and on MECs is described.