Toxic effects of methoxychlor on the episodic prolactin secretory pattern: Possible mediated effects of nitric oxide production

BACKGROUND: This work addresses the issue of whether methoxychlor (MTX) exposure may modify the ultradian secretion of prolactin through changes in the synthesis of nitric oxide (NO) induced by N(ω)-nitro-L-arginine methyl ester (L-NAME) in the hypothalamic-pituitary axis. Associated changes in dopamine (DA) content in the anterior (AH), mediobasal (MBH) and posterior hypothalamus (PH) and median eminence (ME) were evaluated. METHODS: Two groups of animals (MTX and MTX+L-NAME treated) received subcutaneous (sc) injections of MTX at a dose of 25 mg/kg/day for one month. The other two groups of animals (control and L-NAME treated) received sc vehicle injections (0.5 mL/day of sesame oil), during the same period of time to be used as controls. Forty hours before the day of the experiment, animals were anaesthetized with intrapritoneal injections of 2.5% tribromoethanol in saline and atrial cannulas were implanted through the external jugular vein. Plasma was continuously extracted in Hamilton syringes coupled to a peristaltic bomb in tubes containing phosphate-gelatine buffer (to increase viscosity). The plasma was obtained by decantation and kept every 7 minutes for the measurement of plasma prolactin levels through a specific radioimmnunoassay and DA concentration by high-pressure liquid chromatography (HPLC). RESULTS: Prolactin release in animals from all experimental groups analyzed was episodic. Mean plasma prolactin levels during the bleeding period, and the absolute pulse amplitude were increased after MTX or N(ω)-nitro-L-arginine methyl ester (L-NAME) administration. However MTX and L-NAME did not modify any other parameter studied with the exception of relative pulse amplitude in MTX treated rats. L-NAME administration to rats treated with the pesticide reduced mean plasma prolactin levels and the absolute amplitude of prolactin peaks. Peak duration, frequency and relative amplitude of prolactin peaks were not changed in the group of rats treated with MTX plus L-NAME as compared to either control or MTX treated rats. Whereas MTX decreased DA content in the ME and increased it in the AH, its content did not change in the MBH or PH, as compared to the values found in controls. Also, L-NAME administration decreased DA content in the ME as compared to controls. However, L- NAME administration to MTX exposed rats, markedly increased DA content in the ME as compared to either MTX treated or control rats. L-NAME administration increased DA content in the AH as compared to the values found in non-treated rats. However L-NAME administration to MTX exposed rats did not modify DA content as compared to either MTX treated or control rats. L-NAME administration did not modify DA content at the MBH nor in saline treated nor in MTX treated rats. However, the values of DA in the MBH in MTX plus L-NAME treated animals were statistically decreased as compared to L-NAME treated rats. In the PH, L-NAME administration increased DA content as compared to the values found in non-treated animals. L-NAME administration to MTX exposed rats also increased DA content as compared to either MTX treated or control rats. CONCLUSION: The results suggest the existence of an interaction between MTX and L-NAME in the modulation of the ultradian prolactin secretion at the pituitary levels. The possibility of an indirect effect mediated by changes in DA content at the ME requires further examination

Neuroimmunoendocrinology of the cervical autonomic nervous system

This article reviews several peripheral neuroendocrine relationships in the cervical region, namely the effect of the sympathetic innervation on adenohypophysial, thyroid and parathyroid hormone release, and the effect of parasympathetic innervation in thyroid and parathyroid glands. The possible pathways through which the central nervous system modulates the circadian organization of the immune response are also reviewed and the relative importance of circadian control of immune reactivity through local sympathetic and parasympathetic nerves and of neuroendocrine signals, like melatonin, is also discussed. Altogether the present article argues in favor of the concept that nerves arriving to the endocrine and lymphoid tissue constitute alternate pathways through which the brain controls immunoendocrine phenomena.Biomedical Reviews 1998; 9: 47-59

Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats

Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of clinical signs of EAE in Lewis rats

24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone and testosterone in male rats subjected to social isolation

BACKGROUND: This work analyzes the effect of social isolation (a mild stressor) on the 24-h variation of pituitary-testicular function in young Wistar rats, assessed by measuring circulating levels of prolactin, FSH, LH and testosterone. METHODS: Animals were either individually caged or kept in groups (4–5 animals per cage) under a 12:12 h light-dark cycle (lights on at 0800 h) for 30 days starting on day 35 of life. Rats were killed at 4-h intervals during a 24-h cycle, beginning at 0900 h. RESULTS: Isolation brought about a decrease in prolactin, LH and testosterone secretion and an increase of FSH secretion. In isolated rats the 24-h secretory pattern of prolactin and testosterone became modified, i.e., the maximum in prolactin seen in control animals at the beginning of the activity span was no longer detected, whereas the maximum in circulating testosterone taking place at 1700 h in controls was phase-delayed to 2100 h in isolated rats. CONCLUSION: Social isolation affects the 24-h variation of pituitary-testicular function in young rats. Secretion of prolactin, LH and testosterone decreases, and secretion of FSH increases, in isolated rats. The maximum in prolactin seen in group-caged rats at the beginning of the activity span is not observed in isolated rats. The maximum in circulating testosterone taking place at the second part of the rest span in controls is phase-delayed to the light-dark transition in isolated rats

Effect of litter separation on 24-hour rhythmicity of plasma prolactin, follicle-stimulating hormone and luteinizing hormone levels in lactating rabbit does

BACKGROUND: This work describes the effect of a 48-h litter separation on 24-h patterns of plasma prolactin, FSH and LH concentration in female lactating rabbits kept under a 16:8 light-dark photoperiod (lights on at 0800 h). METHODS: Groups of 6–7 female lactating rabbits maintained with their litters or separated from them for 48 h were killed by decapitation on day 11 post-partum, at 6 different time points throughout a 24-h cycle, starting at 0900 h. Plasma levels of prolactin, FSH and LH were measured by specific double antibody radio-immunoassays. RESULTS: Plasma level of prolactin in control and separated does changed in a similar way throughout the day, showing two maxima, at 0500–0900 h and at 1700–2100 h, respectively. Litter separation significantly augmented plasma FSH and LH and disrupted their 24-h rhythmicity. CONCLUSION: Since previous studies had shown that litter separation for short periods of time augmented sexual receptivity and fertility of the doe, the changes in FSH and LH reported may influence the massive release of gonadotropin releasing hormone, LH and FSH triggered by mating or artificial insemination in litter-separated mothers

Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction

Male Lewis rats (6 weeks-old) were submitted to a calorie restriction equivalent to 33% or 66% of food restriction. Fifteen days later, groups of 7 animals were injected with complete Freund's adjuvant plus spinal cord homogenate (SCH) to induce experimental allergic encephalomyelitis (EAE) or with complete Freund's adjuvant alone. EAE was defined solely on clinical grounds. Rats were assessed daily for clinical signs of EAE and were killed on day 15 after immunization. Both diet and SCH injection diminished body weight significantly. In contrast to rats receiving a normal diet or a 33% calorie-restricted diet, rats subjected to severe calorie restriction did not exhibit clinical signs of EAE. Concomitantly with the lack of disease manifestation, 66% of calorie-restricted rats injected with SCH showed significantly less splenic and lymph node mitogenic response to concanavalin A (Con A) and a higher splenic response to lipopolysaccharide. Fewer splenic, lymph node and thymic CD4(+ )cells, greater numbers of splenic and lymph node CD8(+ )and CD4(+)- CD8(+ )cells, and fewer splenic T, B and T-B cells, and lymph node and thymic B and T-B cells were observed. There was impaired interferon (IFN)-γ production occurred in the three examined tissues. The results are compatible with the view that the acute phase of EAE can be curtailed by severe calorie restriction, presumably through impaired IFN-γ production

Effect of rabbit doe-litter separation on 24-hour changes of luteinizing hormone, follicle stimulating hormone and prolactin release in female and male suckling pups

BACKGROUND: The daily pattern of nursing of the rabbit pup by the doe is the most important event in the day for the newborn and is neatly anticipated by them. Such anticipation presumably needs a close correlation with changes in hormones that will allow the pups to develop an appropriate behavior. Although a number of circadian functions have been examined in newborn rabbits, there is no information on 24-h pattern of gonadotropin release or on possible sex-related differences in gonadotropin or prolactin (PRL) release of pups. This study examined the 24-h changes of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in 11 days old suckling female and male rabbits left with the mother or after short-term (i.e., 48 h) doe-litter separation. METHODS: Animals were kept under controlled light-dark cycles (16 h – 8 h; lights on at 08:00 h). On day 9 post partum, groups of 6–7 female or male rabbit pups were separated from their mothers starting at 6 different time intervals in the 24 h cycle. Pups were killed 48 h after separation. At each time interval groups of male or female pups that stayed with the mother were killed as controls. Plasma, LH, FSH and PRL levels were measured by specific radioimmunoassays. RESULTS: In pups kept with their mother plasma FSH and LH maxima occurred at the first and second part of the light phase (at 13:00 and 17:00 – 21:00 h, respectively) (females) or as two peaks for each of the hormones (at 13:00 and 01:00 h) (males). PRL release was similar in female and male rabbit pups kept with their mother, showing a 24-h pattern with two peaks, at 13:00 and 01:00 h, respectively. Mean 24-h values of gonadotropins and PRL did not differ between sexes. Isolation of pups for 48 h augmented circulating gonadotropin and PRL levels and distorted hormone 24-h pattern to a similar extent in both sexes. CONCLUSION: Significant sex differences in 24-h changes in LH and FSH, but not in PRL, release occurred in rabbit pups kept with the doe. Separation of newborn pups from their mother augmented circulating gonadotropin and PRL levels and disrupted 24-h rhythmicity of gonadotropin and PRL release similarly in both sexes. The effect of pups' isolation can be attributed either to a modification of the circadian pacemaker or to a masking effect on some of its output overt rhythms

Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats

Interferon-gamma (IFN-gamma) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. METHODS: Groups of 6-8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-gamma (10(5) IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. RESULTS: A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-gamma-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-gamma administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. CONCLUSION: The data point out an effect of IFN-gamma on the mechanisms responsible for the circadian organization of pituitary hormone release.Fil: Cano, Pilar. No especifíca;Fil: Cardinali, Daniel Pedro. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Jimenez, Vanessa. No especifíca;Fil: Alvarez, Maria P.. Universidad Complutense de Madrid; EspañaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Esquifino, Ana I.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin

Early Appearance of Epicardial Adipose Tissue through Human Development

Background: Epicardial adipose tissue (EAT) is a visceral fat depot with unique anatomic, biomolecular and genetic features. Due to its proximity to the coronary arteries and myocardium, dysfunctional EAT may contribute to the development and progression of cardiovascular and metabolic-related adiposity-based chronic diseases. The aim of this work was to describe, by morphological techniques, the early origin of EAT. Methods: EAT adipogenesis was studied in 41 embryos from 32 gestational days (GD) to 8 gestational weeks (GW) and in 23 fetuses until full term (from 9 to 36 GW). Results: This process comprises five stages. Stage 1 appears as mesenchyme at 33–35 GD. Stage 2 is characterized by angiogenesis at 42–45 GD. Stage 3 covers up to 34 GW with the appearance of small fibers in the extracellular matrix. Stage 4 is visible around the coronary arteries, as multilocular adipocytes in primitive fat lobules, and Stage 5 is present with unilocular adipocytes in the definitive fat lobules. EAT precursor tissue appears as early as the end of the first gestational month in the atrioventricular grooves. Unilocular adipocytes appear at the eighth gestational month. Conclusions: Due to its early origin, plasticity and clinical implications, factors such as maternal health and nutrition might influence EAT early development in consequence