Lymphocyte response to mitogens: influence of life events and personality.

The aim of the present study was to examine the possibility that the accumulation of life events is associated with low lymphoproliferative response to mitogens in undergraduate students. We also analyzed the possible interaction between life events and personality traits. Lymphocyte response to phytohemagglutinin (PHA) was lower in subjects with high life events compared to those with low levels. Introverted subjects were found to exhibit lower lymphocyte responses to PHA than those who were extraverted, and there was no interaction between the effect of introversion and life events on the proliferative capacity. Lymphocyte proliferation was low in subjects with high anxiety scores, whether they had high or low levels of life events. In the group with high scores on independence a high accumulation of life events was not associated with lower lymphoproliferation; while in the group with low scores it was, suggesting that independence buffers the association between life stress and lower cellular immunity.

Short and long restraint differentially affect humoral and cellular immune functions.

The aim of this work was to examine the effect of different periods of restraint on the humoral and cellular immune functions in adult male rats. Short restraint stress (2 h over 2 consecutive days) enhanced the primary serum antibody response to sheep red blood cells. The enhancement of this humoral response was dependent on the restraint period, since long restraint stress (6 h over 4 days) failed to modify this response. Short and long restraint decreased both the number of lymphocytes and the T-lymphocyte response to Con A stimulation in the peripheral blood. Neither 2 h over 2 days nor 6 h over 4 days modified the splenic lymphoproliferative response to Con A stimulation, but restraint stress progressively decreased the number of mononuclear splenic cells. Both periods of restraint significantly increased plasma concentration of corticosterone, however plasma prolactin levels were significantly lower after 4 days of restraint but not after short restraint (2 h over 2 days). These results indicate that although some immune functions can be increased after acute or short stress, long stress has an immunosuppressive effect, above all on the cellular immunity which is more susceptible to this effect than the humoral response.

Restraint-induced changes in serum luteinizing hormone, prolactin, growth hormone and corticosterone levels in rats: effect of superior cervical ganglionectomy.

From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Naltrexone does not reverse the inhibitory effect of chronic restraint on gonadotropin secretion in the intact male rat.

There is considerable evidence suggesting that endogenous opioids may play an important role in acute stress-induced decreases in luteinizing hormone (LH) release. Studies were undertaken to analyze the role of endogenous opioids in chronic stress-induced decrease in circulating LH and follicle-stimulating hormone (FSH). Chronic restraint (6 h daily over 4 days) evoked a decrease in circulating LH and FSH. Naltrexone treatment, (2 mg/kg three times daily) during the 4 days of restraint, caused an increase in plasma concentrations of LH and FSH, and antagonized the LH suppressory effect of morphine (10 mg/kg) administration. Despite this, naltrexone treatment was ineffective in preventing the inhibitory effect of chronic restraint stress on circulating LH and FSH. Chronic restraint also induced a decrease in hypothalamic LH-releasing hormone (LHRH) content in saline-treated rats. On the contrary, in naltrexone-treated rats, chronic restraint evoked an increase in hypothalamic LHRH content. Thus endogenous opioids and chronic stress seem to act by different mechanisms on the hypothalamic LHRH neuron. In unstressed orchidectomized rats, naltrexone administration did not modify circulating LH, but increased plasma concentrations of LH in acutely restrained rats. These data suggest that endogenous opioids may mediate gonadotropin secretion during acute stress, but not during chronic stress.

Stress induced changes in testis function.

The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids.

Role of LHRH in the gonadotrophin response to restraint stress in intact male rats.

A hypothalamic site of action has been hypothesized for the inhibitory effect of chronic stress on gonadotrophin secretion. The aim of the present study was to examine the temporal changes in hypothalamic LHRH content and gonadotrophin secretion during restraint stress, and the pituitary responsiveness to LHRH stimulation in chronically stressed rats. Adult male rats were killed after being restrained for 0, 20, 45, 90, 180 and 360 min or for 6 h daily over 2, 3 and 4 days. After 20-45 min of stress there was an increase in plasma concentrations of LH (P less than 0.01) and a decrease in hypothalamic LHRH content (P less than 0.01), suggesting a negative correlation between plasma LH and hypothalamic LHRH concentrations. Plasma concentrations of FSH were also increased by restraint, but the FSH response was slower and less than the plasma LH response, being significant after 90 min of restraint. Plasma LH and FSH and hypothalamic LHRH concentrations were decreased in chronically stressed rats. In rats restrained for 6 h daily over 4 days, the response of plasma gonadotrophins to administration of 500 ng LHRH was enhanced 45 min after the injection. On the basis of these observations we concluded that in the intact rat, stress may acutely stimulate LHRH and gonadotrophin secretion, and the inhibitory effect of chronic stress on plasma LH and FSH seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a decrease in LHRH secretion.

Tamoxifen decreases the estradiol induced progesterone receptors by interfering with nuclear estrogen receptor accumulation.

The retention time of the estrogen receptor in the nucleus of target cells after antiestrogen treatment has been shown to be longer than after estradiol. This paper describes the accumulation of nuclear estrogen receptors and the obtention of estrogenic responses (i.e. synthesis of cytosolic progesterone receptors and DNA) in the rat uterus after tamoxifen treatment in the presence or absence of estradiol. One-week ovariectomized adult rats were implanted with a silicone elastomer capsule containing corn oil or 25 micrograms estradiol/capsule (0 h). 48 h after implantation rats were injected with corn oil or 2 mg tamoxifen/kg and decapitated at 72, 96 or 120 h after implantation. In parallel experiments the implants were removed just before the injections of tamoxifen or oil. Tamoxifen injected into rats implanted with oil increased both the occupied nuclear receptors and the progesterone receptors at 96 h. In rats implanted with estradiol, tamoxifen did not increase the occupied nuclear receptors and decreased the levels of progesterone receptor and DNA at 96 h. In rats whose estradiol implants were removed at 48 h tamoxifen did not change the level of occupied nuclear receptors at 72 h but it increased them abruptly at 96 and 120 h. In these rats progesterone receptors decreased at 72 h but they increased at 96 and 120 h, and DNA decreased at 120 h to a lower level than before implantation. The results suggest that when estradiol is acting, tamoxifen is not able to increase the level of occupied estrogen receptor and it acts as an antiestrogen by decreasing the high level of progesterone receptors previously induced by estradiol. When estradiol is not acting tamoxifen behaves as a partial estrogen agonist by inducing progesterone receptors. However, the antiestrogenic action of tamoxifen on the rat uterus DNA does not seem to be affected by estradiol.

Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats.

The response of prolactin to chronic stress in intact, adrenalectomized and adrenomedullectomized male rats was studied. Immobilization stress in intact animals induced a significant increase in plasma concentrations of prolactin after 20 and 45 min and a significant decrease when the rats were submitted to chronic restraint (6 h daily for 4 days). Five weeks after adrenomedullectomy, plasma prolactin and corticosterone responses to chronic stress were not modified. In contrast, the inhibitory effect of chronic stress on prolactin secretion was totally suppressed by adrenalectomy. When treated with dexamethasone during the 4 days of restraint, adrenalectomized stressed rats showed similar plasma concentrations of prolactin to the intact stressed rats. These data indicate that the adrenal cortex is able to play an inhibitory role on prolactin secretion during stress only through a prolonged release of glucocorticoids.

Relationship between occupied form of nuclear estrogen receptor and cytosolic progesterone receptor or DNA synthesis in uteri of estradiol implanted rats.

The effect of 17 beta-estradiol (E2) implantation on the cytosolic progesterone receptor (RcP), DNA and occupied form of nuclear estrogen receptor (o- Rn) content in the uterus of ovariectomized adult rats, is described. Animals were implanted with oil or E2-oil solution in Silastic capsules. The latter group animals were divided into two subgroups: in subgroup (a), capsules remained in situ until decapitation time. In subgroup (b) they were removed 48 h after implantation. The E2 implantation caused a significant increase in uterine weight, RcP and o-Rn content 48 h later. However, the DNA content increased significantly only after 72 h, but there was no significant difference in the t-Rn concentration in relation to the non-estrogenized animals. In subgroup (a) animals, these values remained unchanged until 96 h. In subgroup (b), the removal of E2 implants 48 h later caused an almost complete return to the values before the E2 implantation in terms of uterine weight, RcP and o-Rn content. However the DNA concentration remained higher and the t-Rn level was lower than those values that were obtained for the non- estrogenized rats. These results suggest that the RcP and DNA synthesis induced by E2 would be connected to the level of o-Rn, although a closer dependency over time seems to exist between the o-Rn and RcP levels than between the o-Rn and DNA concentrations.

Relationship between unbound oestrogen receptors in the uterus and anterior pituitary gland after implantation of oestradiol-17 beta into rats.

This paper describes the effect of oestradiol-17 beta implants on unbound cytosolic and nuclear oestrogen receptors in the uterus and anterior pituitary gland of ovariectomized adult rats. Rats were ovariectomized and implanted 1 week later with oil or oestradiol-17 beta/oil solution in silicone elastomer capsules. In the latter animals the capsules either remained in situ until decapitation (subgroup 1) or were removed 48 h after implantation (subgroup 2). Implants of oestradiol-17 beta caused a significant depletion in both forms of oestrogen receptor in the uterus and anterior pituitary gland of rats in subgroup 1. In subgroup 2, however, there was an almost complete return to control concentrations of uterine cytosolic receptors and anterior pituitary cytosolic and nuclear receptors. Concentrations of uterine nuclear oestrogen receptors showed only a partial recovery. These data suggest that both forms of oestrogen receptor constitute an integrated population of oestrogen receptors, without dependence on intracellular location, and that in the presence of oestradiol these receptors are bound more quickly than they are synthesized. The results also indicate the existence of a dynamic equilibrium of unbound receptors between the cytosolic and nuclear compartments for both target organs, but show that in the absence of oestradiol this equilibrium is restored in the anterior pituitary sooner than in the uterus.

[Ovarian and adrenal influence on the ontogenesis of uterine cytosol and nuclear receptors of estrogens]. / Influencia ovárica y adrenal en la ontogénesis de los receptores citosólicos y nucleares uterinos de estrógenos.

Adrenal and ovarian relative influence over rat uterus estrogenic receptor, both cytosolic (RcE) and nuclear (RnE) ontogenesis, has been studied. Ovarian influence has been studied by practising bilateral ovariectomy the first day of life and examining estrogenic receptor content evolution from, birth to puberty in these ovariectomized animals (OVX1) by comparison with the normal ones. This influence seems to be of scarce importance until the 20th day of life, since estrogenic receptors content is practically coincident in the OVX1 animals and in the control ones. From the 20th day, ovarian secretion influence increases and estrogenic receptor evolution starts evolving in a different way in the two types of animals. Adrenal influence has been studied by practising bilateral adrenalectomy on the 10th or 30th day of life to OVX1 animals or else OVX and ADX on the 10th or 30th day. Adrenal influence in the upkeep of high estrogen receptor levels on the 10th day, seems to be important, since in the absence of these glands it decreases in a considerable way. The situation is different on the 30th day. At this age ovarian secretion seems to be the most important in maintaining estrogen receptor levels, while adrenal secretion effects tend to inhibit them, especially RnE.