Lee L. Pennington

Comparison of stress response in male and female rats: pituitary cyclic AMP and plasma prolactin, growth hormone and corticosterone.

Three potent stressors (forced running, immobilization, and footshock) were found to increase levels of cyclic AMP in the pituitaries of both female and male rats. The pituitary cyclic AMP response in females was generally similar to that observed in males. The tested stressors elevated both plasma corticosterone and prolactin and decreased plasma growth hormone. Plasma corticosterone rose more rapidly in females than in males following stress. Control growth hormone levels were higher in male rats. There was no clear cause and effect relationship between elevations of pituitary cyclic AMP and changes in plasma levels of prolactin, corticosterone, and growth hormone.

Effects of repeated stress on pituitary cyclic AMP, and plasma prolactin, corticosterone and growth hormone in male rats

The effects of five putative stressors (saline injection, cold exposure, forced running, immobilization, and footshock) on levels of pituitary cyclic AMP, plasma prolactin, corticosterone and growth hormone were examined. In naive rats exposed to 15 min of these stressors for the first time, running, immobilization and footshock increased levels of pituitary cyclic AMP, plasma corticosterone and prolactin and decreased growth hormone, typical of stress response in the rat. Cold exposure only increased corticosterone and saline injection did not affect any measured parameter. In rats chronically exposed to the same stressor (once a day for 15 min) for 10 days immediately prior to the experiment, an attenuated pituitary cyclic AMP and plasma prolactin response was seen upon application of 15 min of that stressor on the day of the experiment, compared to the responses observed in the naive rats.

Graded footshock stress elevates pituitary cyclic AMP and plasma β-endorphin, β-LPH, corticosterone and prolactin

Abstract Male rats were subjected to 15 min of various intensities of footshock current (0.0, 0.2, 0.4, 0.8, 1.6, 2.4, 3.2mA) on a variable interval schedule with an average intershock interval of 30 sec (30 shocks/15 min session). Each shock lasted 5 sec. Animals were sacrificed immediately after being removed from the shock box. Two similar studies were conducted. In the first experiment, rats were sacrificed by microwave irradiation and pituitary cyclic AMP levels were determined. In the second study, rats were decapitated and plasma hormones (prolactin, corticosterone, β-endorphin, β-LPH) were measured by radioimmunoassay. Although all biochemical indices of stress measured increased as shock intensity increased, some differences among the substances measured were observed with respect to threshold intensity, range of proportional response and maximal response.

Specific Hormonal and Neurochemical Responses to Different Stressors

The neuroendocrine and neurochemical responses of rats to 5 min of cold exposure versus 5 min of forced immobilization were determined and compared. We found that plasma hormones and brain neurochemical systems responded differently to the two different stressors. Plasma prolactin levels were elevated over 10-fold in the immolilized group, while rising only 2-fold in the cold stress group. Levels of corticosterone were significantly increased and growth hormone levels were decreased in both stressed groups as compared to controls. Levels of cyclic GMP were markedly elevated in 11 brain regions following cold exposure. Surprisingly, no elevation of cyclic GMP was found after forced immobilization. Cyclic AMP, norepinephrine, and dopamine levels throughout the 17 regions of brain examined showed no significant response to 5 min of either stressor. Lesions of the ventral medial tegmental area did not affect the cyclic GMP or neuroendocrine responses to cold stress. Lesion of the nucleus locus ceruleus did not affect the cyclic GMP response but significantly reduced growth hormone levels in the cold-stressed rats.

The effect of locomotor activity on cerebellar levels of cGMP

Abstract The effect of locomotor activity on brain regional levels of cyclic guanosine 3′, 5′-monophosphate (cGMP) and cyclic adenosine 3′, 5′-monophosphate (cAMP) was examined in rats trained to run in an activity wheel. Following 5 minutes of running, there was a two-fold elevation over control levels of cerebellar cGMP. Significant elevations were seen in eight other regions. No changes were observed in cAMP. Plasma levels of hormones indicative of stress were not significantly different between groups. We suggest that locomotor activity may contribute to elevations in cGMP in cerebellum and other brain regions in rats exposed to a variety of conditions.

Plasma growth hormone response to avoidance sessions in the monkey.

&NA; Plasma immunoreactive growth hormone levels usually rise during conditioned avoidance sessions in monkeys. The rise occurs promptly, being evident in the first sample obtained after avoidance onset (30 min.), and levels remain elevated during 2‐hr. avoidance sessions. Preliminary experiments suggest that the elevations may persist during longer avoidance sessions, but the reliability of single 9: 00 A.M. fasting samples in assessing day‐to‐day changes in growth hormone levels is open to question because of the lability of this system. This study of growth hormone levels is complicated by a high frequency of elevated “baseline” values. It was consistently observed, however, that when “baseline” growth hormone values were below 7 m&mgr;g./ml., levels subsequently rose during avoidance, while when “baseline” values were above 7 m&mgr;g./ml., levels subsequently fell during avoidance sessions. Several lines of evidence are presented which suggest that psychological response to the venipuncture procedure may be a major determinant of “baseline” variability in growth hormone levels. The lability of this system appears to be such that venipuncture effects may occur within the period of a few minutes required for a single venipuncture. Our data so far indicate a normal “basal” plasma immunoreactive growth hormone level in the region of 2 to 3 m&mgr;g./ml. in the rhesus monkey. The significance of the sensitivity of growth hormone secretion to psychological influences is discussed in relation to the study of growth hormone regulation in general.

Plasma insulin response to 72-hr. avoidance sessions in the monkey.

&NA; Plasma immunoreactive insulin levels, determined by radioimmunoassay, show a biphasic pattern of response to avoidance sessions in the monkey. There is an initial drop in plasma immunoreactive insulin levels during the first hours of avoidance and a later prolonged elevation of levels above baseline‐‐persisting often for many days following 72‐hr. avoidance sessions. The fact that the plasma insulin changes in avoidance do not appear to be mediated by changes in plasma glucose levels suggests that other regulatory influences on insulin secretion may supersede blood sugar regulation of insulin levels under some conditions. Some possible mediating mechanisms underlying the observed suppression of plasma insulin levels are discussed. Some evidence is presented that emotional reactions to venipuncture may also elicit a decrease in plasma immuno‐reactive insulin levels with associated elevations in plasma 17‐OHCS and glucose levels.

Plasma Growth Hormone and Cortisol Changes Following Limbic Stimulation in Conscious Monkeys

Electrical stimulation of the amygdaloid nuclei in conscious monkeys sufficient to produce after-discharge was found also to produce a prompt and usually large increase in plasma growth hormone (GH) levels if prestimulation values were low and stable. Plasma GH responses were observed to parallel and slightly precede changes in serum cortisol. Stimulation of the temporal tip of the hippocampus, just posterior to the amygdala, did not produce elevations of GH or cortisol despite the spread of after-discharge activity to the amygdala.

Brain and Pituitary Cyclic Nucleotide Response to Stress

Publisher Summary Endocrine responses to stress have been studied, and several brain neurochemical systems have been shown to be responsive to stress. Stress activates central noradrenergic, dopaminergic, and serotonergic neurons. Noradrenergic stimulation is a potent elevator of brain cyclic adenosine 3′5′ monophosphate (cyclic AMP) in vitro. Cyclic nucleotides in brain function as second messengers, mediating cellular responses to neurotransmitters by activating enzymes, which phosphorylate specific membrane proteins. Brain cyclic AMP increases following stress. Cyclic AMP mediates pituitary responses to humoral stimulation in vitro. Cyclic guanosine monophosphate (GMP) levels in the cerebellum and in a number of other brain regions are not influenced by stress, but by the amount of locomotor activity elicited by the experimental situation. This chapter presents a useful model for assessment of in vivo biochemical responses to stress at the pituitary level. This model is used to compare the responses of pituitary to a variety of acute and chronic stressors and to elucidate the mechanisms of neuronal and neurotransmitter regulation of pituitary response.

Plasma Growth Hormone Response to Capture and Venipuncture in Caged Monkeys

Summary A large percentage of very high plasma immunoreactive growth hormone values was observed in cage-housed rhesus monkeys after net capture and manual restraint for saphenous venipuncture during about a 5-min period. Following chair restraint, mean values were significantly lower, but individual values were still somewhat variable apparently in relation to saphenous venipuncture alone, as judged by lower and less variable values obtained by means of remote blood sampling through chronic indwelling venous catheters. The present findings suggesting marked plasma growth hormone responses in the monkey to net capture, handling, and venipuncture, occurring within about a 5-min period, add emphasis to the need to consider not only the sensitivity of this endocrine system to psychological influences, but also the rapidity with which psychoendocrine responses may be reflected in growth hormone levels, even within the time of a single venipuncture.