Ovarian hormones and food intake in female guinea pigs and rhesus monkeys

Food intake was measured during ovarian cycles of female guinea pigs and rhesus monkeys. In both species, the period of lowest food intake occurred around the expected time of ovulation. Feeding levels were lowest in the guinea pig during the time of estrus, estrus being estimated on the basis of vaginal membrane changes. Minimum food intake in the rhesus occurred prior to the midpoint of the menstrual cycle, on Day 13, approximately 15–16 days before the next menstruation. In ovariectomized females of both species, either multiple or single estradiol injections significantly lowered food intake. Single progesterone injections to such females were found to have no significant effect on levels of feeding.     

Bronchial responsiveness and inflammation in guinea pigs exposed to acrolein

Bronchial hyperresponsiveness can be produced experimentally after inhalation of numerous nonimmunospecific stimuli; our objective was to determine whether acrolein, a component of cigarette smoke, could increase bronchial reactivity to intravenously administered acetylcholine in guinea pigs. Bronchial responsiveness was assessed twice before and 1, 2, 6, and 24 h after exposures to less than or equal to 0.01 (sham), 0.31, 0.67, 0.94, or 1.26 parts per million for 2 h (5-7 guinea pigs/group). To examine the possible relationships of responsiveness to inflammatory mediator release and cellular infiltration, bronchoalveolar lavage was performed in another 30 guinea pigs before (control) and 0, 1, 2, 6, or 24 h after exposures. Pulmonary resistance was increased immediately after exposure (5 min) and returned to control values within 30-60 min. Increased bronchial responsiveness was evident within 1 h and became maximal 2-4 h after exposure. The acetylcholine dose necessary to double resistance decreased from 104.2 +/- 7.3 to 79.6 +/- 15.9 at 1 h and was 32.5 +/- 7.9 at 2 h and 32.8 +/- 7.6 micrograms.kg-1 at 6 h. Increases in two eicosanoids, thromboxane B2 (from 167 +/- 21 to 314 +/- 77 pg/ml) and prostaglandin F2 alpha (from 98 +/- 20 to 285 +/- 62 pg/ml) occurred immediately after exposure, whereas an influx of neutrophils occurred 24 h later (from 2.2 +/- 1.2 to 11.3 +/- 3.6%). These temporal relationships suggest that neutrophil infiltration may be a sufficient but not a necessary condition for the onset of bronchial hyperresponsiveness and that injury to cells normally present in the lung are responsible for the mediators thought to influence bronchial responsiveness.     

Ultrastructural changes of sebaceous glands in castrated and testosterone-treated male rats

Summary The effect of testosterone on the sebaceous gland was studied in the male rat. Biopsies of dorsal skin from intact rats, from rats four weeks after castration, and from castrated rats treated with testosterone propionate for three weeks at a dose of 250 g/kg/day (s.c.) were examined by electron microscopy. In the treated animals intermediate sacrifices were performed on days 4,7,14,21. Stereology was used for a morphometric analysis of the smooth endoplasmic reticulum (SER). The presence of a vesicular endoplasmic reticulum throughout the cytoplasm of differentiating cells was observed in the sebaceous glands of intact rats. Following castration there was a shrinkage of these cells and a striking decrease in the volume density of the endoplasmic reticulum vesicles. The administration of testosterone to gonadectomized rats resulted in an increase in vesicle content above the normal level from the first week as revealed by stereological analysis. This study confirms the trophic effect of the androgen on the sebaceous gland at a subcellular level. Furthermore, it is shown that stereology is a useful method for detecting early hormone-induced changes and could be valuable for studying the effects of anti-androgens on this gland.     

Airway responsiveness and prostaglandin generation in scorbutic guinea pigs

Airway responsiveness to histamine aerosol and lung prostaglandin generation were investigated in normal, partially vitamin C deficient and scorbutic guinea pigs. The ascorbic acid content of the lung expressed as microgram/100 mg wet weight lung parenchyma decreased from 22.1 +/- 1.8 (mean +/- SE) in the control group to 9.0 +/- 1.4 and 1.8 +/- 0.4 in tissues from partially ascorbic acid deficient and scorbutic animals, respectively. Guinea pigs on low and ascorbic acid deficient diets developed significant airway hyperresponsiveness to histamine aerosol after 3 and 4 weeks. Indomethacin (30 mg/Kg, i.p.) further increased the airway hyperresponsiveness in scorbutic animals but was without effect in control animals. Prostaglandin generation from different parts of the lung was significantly changed by the diets. However, airway hyperresponsiveness was not directly attributable to altered prostanoid generation. Scorbutic conditions did not alter the electrophysiological characteristics of airway smooth muscle namely, resting membrane potential and electrogenic sodium pump activity. In summary, ascorbic acid deficiency causes airway hyperresponsiveness to histamine in guinea pigs. This alteration seems not to be related to an altered prostaglandin generation by the lung or to the electrophysiological properties of airway smooth muscle.     

Uterine position and the activation of male sexual activity in testosterone propionate-treated female guinea pigs

Fetal female guinea pigs were delivered surgically and their position within a uterine horn relative to male fetuses was noted. When adult they were ovariectomized, injected daily with testosterone propionate, and examined for male copulatory behaviors in response to the presence of a receptive female. Females that developed contiguous to a caudal male were functionally similar to those that had been situated between two males; both exhibited enhanced levels of mounting relative to females that were located contiguous to no males (with and without the presence of a caudal male) and to females contiguous to a cephalic male. Therefore, both contiguity and positioning of the male fetus are necessary conditions for prenatal masculinization of the female guinea pig. Lastly, four animals that had resided singly in the uterus displayed the lowest levels of copulatory behaviors.     

Somatic antigens from male and female adults of Setaria cervi: immune reactions in guinea pigs

Antigens obtained from adult female Setaria cervi were more protective than those of males against the development of microfilaremia in guinea pigs (transplanted with 10 S. cervi). In high dose levels (2 ml 500 microliters/ml) significant resistance was induced by antigens from male (52% of protection) and female (62% of protection) worms. The antigens from female worms were effective (40% protection) at low dose level (2 ml 50 microliters/ml) also.     

The effect of urine from castrated male or female guinea pigs and rats on the estrous cycle of guinea pigs and rats, respectively]

A 24-hour reduced cycle duration was observed in 5-day cyclic female rats exposed to the odor of urine from male or female castrated rats. A decrease in the duration of the period of vaginal closure, ranging from 2 to 5 days, was observed in female guinea pigs exposed to the odor of urine from male or female castrated guinea pigs. The pheromonal activity of urine in both species was concluded to be no dependent upon the gonadal function.     

Differential responsiveness of LH and prolactin to p-tyramine in male and female rats

The effect of p-tyramine, a natural amine which is found in the rat brain in trace amounts, was evaluated for its capacity to influence LH and prolactin secretion in male and female rats under different hormonal conditions. p-Tyramine (40 mg/kg ip) was ineffective in modifying LH levels in either female or male rats which had been gonadectomized for 2 days, but if the animals were injected with 12.5 micrograms of estradiol benzoate (EB) on the day of castration, p-tyramine was able to release LH in female but not in male rats. To evaluate whether early androgenization of brain structures which control LH secretion was involved in the sexual difference observed, p-tyramine was tested in female androgenized rats (200 micrograms of testosterone propionate on the day of birth), and in male rats castrated at birth. The trace amine was ineffective in altering LH levels in both experimental models, even if rats were pretreated with EB as control females. On the other hand, p-tyramine inhibited prolactin secretion in male rats pretreated with EB, and not in similarly treated female rats. The present results suggest that p-tyramine may be involved not only in prolactin regulation as it has been previously shown, but also in LH control, and that the hormonal response to this amine is sexually differentiated in the rat.     

Reduced anaphylactic responsiveness of strain 2 guinea pigs.

Strain 2 guinea pigs have been shown to have diminished anaphylactic responsiveness. In the present study, experiments were conducted comparing various characteristics of the anaphylaxis-resistant Strain 2 guinea pigs to those of an outbred anaphylaxis-prone Dunkin-Hartley strain. To bypass the possibility that differences in antibody titers accounted for the difference in anaphylactic reactivity, both strains of guinea pig were passively sensitized with the same amount of IgG antibody to ovalbumin. Measures of anaphylactic responsiveness to subsequent antigen challenge with ovalbumin included (i) systemically induced respiratory responses; (ii) isolated cardiac responses; and (iii) cutaneous responses. In all cases, using an amount of antibody sufficient to sensitize Dunkin-Hartley guinea pigs, the anaphylactic responses of the Strain 2 guinea pigs were either nonexistent or significantly less than those of the Dunkin-Hartley strain. To further determine which factors might be responsible for this difference, tissue histamine content, histamine releasability, and histamine responsiveness of the two strains were measured. The results of these studies indicated that the respiratory hyporesponsiveness of the Strain 2 guinea pigs may be due to a low pulmonary histamine content combined with reduced pulmonary responsiveness to histamine. However, since the cardiac histamine content and the responsiveness of the Strain 2 guinea pigs were not different from those of the Dunkin-Hartley strain, these factors cannot contribute to the reduced Strain 2 cardiac anaphylactic responsiveness. Compound 48/80 released equal quantities of histamine from the isolated hearts of the Strain 2 and the Dunkin-Hartley animals, but antigen challenge evoked histamine release only from the isolated Dunkin-Hartley hearts. We conclude that the cardiac anaphylactic hyporesponsiveness of the Strain 2 guinea pigs may be due to an inability of antigen to evoke release of anaphylactic mediators such as histamine.     

Comparative study of the pulmonary effects of intravenous leukotrienes and other bronchoconstrictors in anaesthetized guinea pigs

Pulmonary responses to intravenous leukotrienes C4, D4 and E4 administered as a bolus injection and by continuous infusion were studied in anesthetized guinea pigs. LTD4, LTC4 and LTE4 (respective ED50 of 0.21 +/- .1, 0.64 +/- .2 and 2.0 +/- .1 microgram kg-1) produced dose-dependent increases in insufflation pressure when given as a bolus injection to anesthetized guinea pigs (Konzett-R?ssler). Bronchoconstriction was antagonized by FPL-55712 (50-200 micrograms kg-1), and indomethacin (50-200 micrograms kg-1) but was not significantly altered by mepyramine (1.0 mg kg-1), methysergide (0.1 mg kg-1), intal (10 mg kg-1) mepacrine (5 mg kg-1) or dexamethasone (10 mg kg-1). The beta adrenoceptor blocker, timolol (5 micrograms kg-1) produced a significantly greater potentiation of the responses to the leukotrienes than to arachidonic acid, histamine and acetylcholine. Responses to bolus injection of LTE4 but not LTD4 or LTC4 were partially antagonized by atropine (100 micrograms kg-1) and bilateral vagotomy. In experiments of a different design, continuous infusion of LTD4 and LTE4 (2.8-3.2 micrograms kg-1 min-1) into indomethacin-treated animals produced slowly developing increases in pulmonary resistance and decreases in compliance. The increase in resistance produced by LTE4 and LTD4 was partly reversed by intravenous FPL-55712 (1.0 mg kg-1) and atropine (100 micrograms kg-1) but was almost completely reversed by FPL-55712 (3 - 10 mg kg-1). These findings indicate that leukotrienes can produce bronchoconstriction in guinea pigs through cyclooxygenase-dependent and cyclooxygenase independent mechanisms both of which are blocked by FPL-55712. Cholinergic mechanisms are involved in the mediation of part of the response to bolus injection of LTE4 as well as a small part of the initial response to continuous infusion of LTD4 and LTE4. Intrinsic beta adrenoceptor activation serves to down modulate responses to the leukotrienes to a greater extent than responses to arachidonic acid, histamine and acetylcholine.     

Inhaled bordetella pertussis vaccine decreases airway responsiveness in guinea pigs

Bordetella pertussis (BP) has been used as adjuvant for experimental animal immunization, but its effects on airway responsiveness are uncertain. Three groups of guinea pigs were used: animals with a single exposure to inhaled BP vaccine (strain 134, total dose 1.24 × 10¹²germs), animals submitted to a sensitization procedure through inhalation of ovalbumin plus BP and healthy control animals. Four weeks after inhalation of BP or after the beginning of sensitization, dose- or concentration-response curves to histamine were constructed in vivo and in vitro (tracheal and parenchymal preparations). We found that BP alone produced lower responses to histamine than control guinea pigs in vivo (insufflation pressure, p = 0.0003) and in tracheal tissues (p = 0.04), but not in parenchymal preparations. Sensitization did not modify the responsiveness compared with their respective controls. These results suggest that some BP component(s), probably pertussis toxin, causes a long lasting airway hyporesponsiveness in guinea pigs.     

Oestrogen-progestin regulation of female sexual behavior in guinea pigs

The display of female sexual behavior in guinea pigs is strongly correlated with the concentration of cytoplasmic progestin receptors in hypothalamic-preoptic area-septum (HPS). These progestin receptors increase in concentration in the HPS after a period of oestrogen priming. The synergistic actions of oestrogen and progestin may not only influence noradrenergic transmission, but noradrenergic transmission may influence the degree of synergy between oestrogen and progestin.     

Effects of natalizumab,an α4 integrin inhibitor,on fertility in male and female guinea pigs

BACKGROUND : Natalizumab is a humanized monoclonal immunoglobulin G4 antibody directed against the human α4 integrin subunit disrupting interaction with its ligands. As α4 integrins and/or their ligands appear to be involved in reproductive function, the effects of natalizumab on fertility in male and female guinea pigs were investigated. METHODS : Natalizumab was administered by bolus intravenous injection every other day at doses of 0, 3, 10, and 30 mg/kg. Males began treatment at least 28 days prior to mating until necropsy (approximately 3 to 5 days after mating). Dosing in females was done from gestational day (GD) of an existing pregnancy to GD 30 of a second pregnancy. RESULTS : In male guinea pigs, natalizumab treatment had no effect on sperm parameters, reproductive organ weights, organ-weight ratios, or histology of the testis or epididymis. Natalizumab did not affect the ability of treated males to produce pregnancies in untreated females. In female guinea pigs, no treatment-related changes were seen in uterine weights or ovary weights. Pregnancy rates were reduced in females treated with 30 mg/kg natalizumab, but not those treated with 3 or 10 mg/kg. Pregnancy rates were 63.3, 66.7, 66.7, and 29.6% for groups treated with 0, 3, 10, and 30 mg/kg, respectively. Effects observed at 30 mg/kg were at exposures 36-fold those observed in humans. CONCLUSIONS : Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with the high dose of 30 mg/kg. Birth Defects Res (Part B)86: 108-116, 2009. © 2009 Wiley-Liss, Inc.