Luteinizing hormone-releasing hormone in olfactory bulbs of primates

This immunohistochemical study of luteinizing hormone-releasing hormone (LHRH) in the olfactory bulbs in primates was undertaken in order to see whether there was an LHRH innervation in these species similar to that found in rodents. One old world (Macaca fascicularis) and two new world (Saimiri sciureus and Aotus trivirgatus) monkeys were studied. Aotus trivirgatus was of particular interest as it is noctural and so presumably more dependent upon olfactory cues. Animals were perfused with fixative, olfactory bulbs removed and sectioned, and tissues reacted immunocytochemically using LR1 (Benoit) antiserum to LHRH. Some LHRH innervation was found in the olfactory bulbs of all three species, comprising a few LHRH neurons and many fibers that ramified within the bulbs. The accessory bulb (not present as a distinct entity in old world primates) had more LHRH innervation than did the main olfactory bulb. Aotus trivirgatus had the greatest representation of LHRH of the three species. The layer of the olfactory bulb with the greatest number of LHRH fibers was the external plexiform layer. This is also true in rodents. There is evidence that LHRH has a role in the mediation of olfactory cues in reproductive behavior in rodents. It is not known how LHRH functions within the olfactory system in primates. However, the fact that it is distributed similarly in the two groups suggests that it may serve a similar function.     

The 60- and 70-kDa heat-shock proteins and their correlation with cardiovascular risk factors in postmenopausal women with metabolic syndrome

We investigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age ≥45 years with amenorrhea ≥12 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) ≥88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose ≥100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected. HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels were measured in serum. Student''s t test, Kruskal–Wallis test, chi-square test, and Pearson correlation were used for statistical analysis. Of the 311 women, 30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese with abdominal fat deposition and had lower HDL values as well as higher triglycerides and glucose levels. Homeostasis model assessment-insulin resistant (HOMA-IR) test values in these women were compatible with insulin resistance (P < 0.05). CRP and HSP60 concentrations were higher in women with MetS than in women without MetS (P < 0.05). HSP60, anti-HSP70, and CRP concentrations increased with the number of features indicative of MetS (P < 0.05). There was a significant positive correlation between anti-HSP70 and WC, blood pressure and HOMA-IR, and between CRP and WC, blood pressure, glucose, HOMA-IR, and triglycerides (P < 0.05). In postmenopausal women, serum HSP60 and anti-HSP70 concentrations increased with accumulating features of the metabolic syndrome. These results suggest a greater immune activation that is associated with cardiovascular risk in postmenopausal women with metabolic syndrome.     

Influence of complement depletion on sperm function in the female rabbit

Female rabbits were wholly depleted of complement by treatment with anti-complementary cobra venom factor (CVF) 36 h before mating. Complement depletion did not compromise occurrence of the acrosome reaction, as judged by sperm penetration of eggs collected 12-13 h post coitum. However, in CVF-treated females, significantly more spermatozoa had penetrated the egg vestments, more spermatozoa were present in flushings from the oviducts, and sometimes the uterus, than in control females mated to the same males. The results indicate that, although the acrosome reaction is unlikely to depend on complement activation, complement-dependent factors may exert a restrictive effect on spermatozoa after vaginal insemination of the normal female rabbit.     

Expression of Rab3D N135I Inhibits Regulated Secretion of ACTH in AtT-20 Cells

Rab proteins are small molecular weight GTPases that control vesicular traffic in eucaryotic cells. A subset of Rab proteins, the Rab3 proteins are thought to play an important role in regulated exocytosis of vesicles. In transfected AtT-20 cells expressing wild-type Rab3D, we find that a fraction of the protein is associated with dense core granules. In the same cells, expression of a mutated isoform of Rab3D, Rab3D N135I, inhibits positioning of dense core granules near the plasma membrane, blocks regulated secretion of mature ACTH, and impairs association of Rab3A to membranes. Expression of Rab3D N135I does not change the levels of ACTH precursor or the efficiency with which the precursor is processed into ACTH hormone and packaged into dense core granules. We also find that cells expressing mutated Rab3D differentiate to the same extent as untransfected AtT-20 cells. We conclude that expression of Rab3D N135I specifically impairs late membrane trafficking events necessary for ACTH hormone secretion.     

Behavioral effects and benzodiazepine antagonist activity of Ro 15-1788 (flumazepil) in pigeons

The selective benzodiazepine receptor antagonist, Ro 15-1788, produced behavioral effects in pigeons at doses at least 100 times lower than those previously reported to possess intrinsic pharmacological activity in mammals. In contrast to its effects in mammalian species, in pigeons, Ro 15-1788 does not exhibit partial agonist activity. Key-peck responses of pigeons were studied under a multiple fixed-interval 3-min, fixed-interval 3-min schedule in which the first response after 3-min produced food in the presence of red or white keylights. In addition, every 30th response during the red keylight produced a brief electric shock (punishment). Under control conditions, punished responding was suppressed to 30% of unpunished response levels. Ro 15-1788 (0.01 mg/kg, i.m.) increased unpunished response rates by 33% without affecting rates of punished responding. Doses of 0.1 to 1.0 mg/kg Ro 15-1788 produced dose-related decreases in both punished and unpunished responding. As is characteristic of other benzodiazepines, midazolam (0.1 and 0.3 mg/kg, i.m.) markedly increased punished responding but had little effect on rates of unpunished responding. Ro 15-1788 antagonized the increases in punished responding and also reversed the rate-decreasing effects of higher doses of midazolam. However, the effectiveness of Ro 15-1788 as a benzodiazepine antagonist was limited by its intrinsic activity: rate-decreasing doses of Ro 15-1788 were unable to completely reverse behavioral effects of midazolam. Midazolam was an effective antagonist of the behavioral effects of Ro 15-1788 (up to 0.1 mg/kg) but midazolam did not influence the rate-decreasing effects of 1.0 mg/kg Ro 15-1788 across a 100-fold dose range. In the pigeon, the behavioral effects of relatively low doses of Ro 15-1788 (0.01-0.1 mg/kg) appear to be related to benzodiazepine receptor mechanisms, whereas other systems appear to be involved in the effects of higher doses.