Role Of Adrenal Hormones Research Articles

Comorbidity of chronic pancreatitis and metabolic syndrome: mechanisms of development

In this article, the authors analyze a number of known and probable mechanisms involved in the formation of metabolic disorders upon chronic pancreatitis in comorbidity with metabolic syndrome. The issue of involvement of pancreatic endocrine apparatus in development of insulin resistance upon chronic pancreatitis, namely, the role of such a hormone as insulin, is highlighted. The role of this hormone in development of disorders of fat metabolism, obesity and arterial hypertension is presented. The authors emphasize the role of adrenal hormones, estrogen in the pathogenesis of both diseases. The issue of effect of endocrine function disorders on the state of external pancreatic secretion with subsequent development of disorders in the microbiota composition is considered (which also contributes to the progression of both diseases).
 The data on presence of a possible relationship between the composition, functional activity of the intestinal microbiota and development of metabolic syndrome, chronic pancreatitis are given. The significance of intestinal microbiota in the maintenance of various vital processes of a healthy person, food digestion, as well as synthesis, metabolism, recycling, utilization of various biologically active substances (vitamins, hormones, steroids, immunoglobulins) and elimination of toxins is revealed. The role of microorganisms in the formation of feeding behavior via axis “intestinal microbiome — intestine — brain” is analyzed. Modern ideas on the ability of microorganisms to provoke formation of metabolic disorders upon chronic pancreatitis are presented. The data confirming connection of certain dysbiotic changes (increased ratio of Firmicutes/Bacteroidetes, reduced number of Bacteroidetes and increased number of Firmicutes) with development of obesity, overweight, type 2 diabetes mellitus (known risk factors of metabolic syndrome) is given. It is suggested to prevent formation of metabolic syndrome in chronic pancreatitis by increasing the number of specimens of Bifidobacterium genus and Faecalibacteriumprausnitzii strains in the intestine.

Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders.

Hypotension following Patent Ductus Arteriosus Ligation: The Role of Adrenal Hormones

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0μg/kg) stimulation test (performed before the ligation), and at 10-12hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1×dopamine [μg/kg/min]+1×dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P=.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.

Disfunción eréctil de origen hormonal

The proper function of erection mechanisms depend on correct interrelationship between psychological, vascular, neurological and hormonal factors. Endocrine diseases affect sexual function, and sexual dysfunction may be one of the symptoms of some hormonal anomalies. Diabetes mellitus is the endocrine disease most frequently causing erectile dysfunction due to the frequent vascular and neurological complications associated. It is important to determine blood glucose in the initial evaluation of a male with erectile dysfunction, as well as to try an adequate control of blood glucose levels to avoid worsening. Diabetic male erectile dysfunction is multifactorial, more severe and has worse response to oral treatment. Hyperprolactinemia causes disorders of the sexual sphere because it produces a descent of testosterone. In these cases, sexual symptoms are treated by correcting the levels of prolactin. Routine determination of prolactin is not clear and it seems it should be determined when testosterone levels are diminished. Thyroid hormone disorders (both hyper and hypotyroidism) are associated with erectile dysfunction, which will subside in half the patients with thyroid hormone normalization. The role of adrenal hormones in erectile function is not clear and their routine determination is not considered in the diagnostic evaluation of erectile dysfunction. The role of estradiol in the regulation of the erection mechanism is not well known either, although it is known that high levels may cause erectile dysfunction. Among endocrine-metabolic disorders we point out dyslipemias, with hypercholesterolemia as an important risk factor for erectile dysfunction and, though its correction may prevent vascular system deterioration, the role of statins in erectile dysfunction is not clear.

Long-term Survival and Occasional Regression of Distant Melanoma Metastases after Adrenal Metastasectomy

Human melanoma cells express high-affinity glucocorticoid receptors, and adrenalectomy has been shown to have antimelanoma effects in animal models. Long-term regression of distant metastatic melanoma was observed in one patient after bilateral adrenalectomy, prompting a review of adrenalectomy for melanoma metastases performed at this center. A retrospective study in which all patients treated at the Sydney Melanoma Unit and recorded as having adrenal gland metastases between January 1987 and January 2004 were identified and their survival analyzed. One hundred eighty-six patients with adrenal gland metastases were identified. Adrenalectomy was performed in 23 patients; the other 163 patients were treated nonsurgically. The adrenal glands were the sole site of disease in five patients. All symptomatic patients were free of pain after recovery from the surgical procedure. Thirteen patients were rendered clinically and radiologically disease-free by their surgery. There was no postoperative mortality within 30 days. Median overall survival after adrenalectomy was 16 months (2-year survival, 39%), compared with 5 months for patients with documented adrenal metastases treated nonsurgically (P < .00001). In one patient, nonresected visceral metastases elsewhere regressed completely after bilateral adrenalectomy; he remained well and free of disease 80 months after adrenalectomy. Regression of distant visceral metastatic disease also occurred in a second patient after unilateral adrenalectomy. Adrenalectomy for melanoma metastatic to the adrenal gland provides good palliation of symptoms and is associated with prolonged survival in a selected cohort of patients. We report for the first time sustained complete regression of distant metastatic melanoma after bilateral adrenalectomy, suggesting a possible role for adrenal hormones in modifying melanoma progression in certain patients.

Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Long-term survival and disease regression after adrenalectomy for adrenal metastases from melanoma

7540 Background: Human melanoma cells express high affinity glucocorticoid receptors, and adrenalectomy has been shown to have anti-melanoma effects in animal models. We observed long-term regression of metastatic melanoma in two patients following bilateral adrenalectomy, prompting a review of adrenalectomy at the Sydney Melanoma Unit (SMU). Methods: All SMU patients having adrenalectomy for melanoma metastatic to the adrenal gland(s) between January 1987 and June 2001 were identified and examined. Results: 17 patients underwent adrenalectomy for adrenal metastases, 5 females and 12 males, median age 62 years. The adrenal gland(s) were the sole site of disease in 13 patients. Indications were pain (n=4), or the detection of bulky metastases on radiological imaging (n=13). Five patients had bilateral adrenal metastases resected. Significant post-operative morbidity occurred in 2 patients (12%), but there was no post-operative mortality. The median survival of patients after adrenalectomy was 19 months (2 year survival 46%), compared with 4 months for patients with documented adrenal metastases concurrently treated with best supportive care (n=127) (p=0.0001). In two patients non-resected metastases elsewhere regressed following bilateral adrenalectomy, and both remain disease free over three years later. Conclusion: As previously reported, adrenalectomy for adrenal melanoma metastases is associated with prolonged survival in selected patients. We report for the first time sustained complete regression of distant metastatic melanoma following adrenalectomy, suggesting a possible role for adrenal hormones in modifying melanoma in certain patients. No significant financial relationships to disclose.

Long-term survival and disease regression after adrenalectomy for adrenal metastases from melanoma

7540 Background: Human melanoma cells express high affinity glucocorticoid receptors, and adrenalectomy has been shown to have anti-melanoma effects in animal models. We observed long-term regression of metastatic melanoma in two patients following bilateral adrenalectomy, prompting a review of adrenalectomy at the Sydney Melanoma Unit (SMU). Methods: All SMU patients having adrenalectomy for melanoma metastatic to the adrenal gland(s) between January 1987 and June 2001 were identified and examined. Results: 17 patients underwent adrenalectomy for adrenal metastases, 5 females and 12 males, median age 62 years. The adrenal gland(s) were the sole site of disease in 13 patients. Indications were pain (n=4), or the detection of bulky metastases on radiological imaging (n=13). Five patients had bilateral adrenal metastases resected. Significant post-operative morbidity occurred in 2 patients (12%), but there was no post-operative mortality. The median survival of patients after adrenalectomy was 19 months (2 year survival 46%), compared with 4 months for patients with documented adrenal metastases concurrently treated with best supportive care (n=127) (p=0.0001). In two patients non-resected metastases elsewhere regressed following bilateral adrenalectomy, and both remain disease free over three years later. Conclusion: As previously reported, adrenalectomy for adrenal melanoma metastases is associated with prolonged survival in selected patients. We report for the first time sustained complete regression of distant metastatic melanoma following adrenalectomy, suggesting a possible role for adrenal hormones in modifying melanoma in certain patients. No significant financial relationships to disclose.

The role of adrenal hormones in the response of glutamine synthetase to fasting in adult and old rats

Background & Aims: During fasting, skeletal muscle exports increased amounts of glutamine (Gln) while increasing the production of this amino acid by glutamine synthetase (GS) in order to maintain the intramuscular Gln pool. Glucocorticoid hormones are believed to be the principal mediators of GS induction during stress conditions. The aim of this study was to evaluate (1) the effect of fasting on GS activity and expression in skeletal muscle during aging and consequently, (2) the role of glucocorticoids in fasting-induced GS activity. Methods: Male Wistar rats (6-, 22-month old) were fasted for 5 days and both the activity and expression of GS were measured in tibialis anterior muscle. To better demonstrate the role of glucocorticoids in the response of GS to fasting, we suppressed their action by RU38486 administration (a potent glucocorticoid antagonist) and their production by adrenalectomy in fed and fasted rats. Results: An increase in fasting-induced GS activity was observed in skeletal muscles from both adult and aged rats. Adrenalectomy, but surprisingly not RU38486, suppressed the fasting-induced increase in GS activity and expression. Conclusion: The data clearly show that the GS responsiveness to fasting was not modified by aging in skeletal muscle.

Reversal of cycloheximide-induced memory disruption by AIT-082 (Neotrofin) is modulated by, but not dependent on, adrenal hormones.

AIT-082 (Neotrofin), a hypoxanthine derivative, has been shown to improve memory in both animals and humans. In animals, adrenal hormones modulate the efficacy of many memory-enhancing compounds, including piracetam and tacrine (Cognex). To investigate the role of adrenal hormones in the memory-enhancing action of AIT-082. Plasma levels of adrenal hormones (corticosterone and aldosterone) in mice were significantly reduced by surgical or chemical (aminoglutethimide) adrenalectomy or significantly elevated by oral administration of corticosterone. The effects of these hormone level manipulations on the memory-enhancing activity of AIT-082 and piracetam were evaluated using a cycloheximide-induced amnesia/passive avoidance model. As previously reported by others, the memory enhancing action of piracetam was abolished by adrenalectomy. In contrast, the memory enhancement by 60 mg/kg AIT-082 (IP) was unaffected. However, a sub-threshold dose of AIT-082 (0.1 mg/kg, IP) that did not improve memory in control animals did improve memory in adrenalectomized animals. These data suggested that, similar to piracetam and tacrine, the memory enhancing action of AIT-082 might be inhibited by high levels of adrenal hormones. As expected, corticosterone (30 and 100 mg/kg) inhibited the action of piracetam, however no dose up to 100 mg/kg corticosterone inhibited the activity of AIT-082. These data suggest that while AIT-082 function is not dependent on adrenal hormones, it is modulated by them. That memory enhancement by AIT-082 was not inhibited by high plasma corticosterone levels may have positive implications for its clinical utility, given that many Alzheimer's disease patients have elevated plasma cortisol levels.

Stress-induced cross-sensitization to cocaine: effect of adrenalectomy and corticosterone after short- and long-term withdrawal.

We have recently shown that adrenalectomy (ADX) in rats blocks the appearance of cocaine-induced sensitization when this behavioral response is tested at early withdrawal times (1-2 days), but not after later withdrawal from cocaine (12 days). To determine if a similar phenomenon occurred with stress-induced sensitization, male Sprague-Dawley rats were given a sham ADX, ADX surgery, or ADX plus s.c. implanted corticosterone (CORT) pellets (CORT 12.5% pellets or CORT 50% pellets). A fifth group was given ADX surgery, but CORT 50% pellets were implanted after repeated stress treatment. One week after surgery, each group was divided into two additional groups, naive and stress. Naive animals remained unhandled, while stress rats were given a variety of daily stressors administered twice per day for 6 consecutive days. One day after the last stress, rats were given a saline injection followed by a cocaine injection (15 mg/kg, i.p.) the next day, and locomotor activity was monitored (early withdrawal). Two weeks after the last stress, the locomotor responses to an additional saline and cocaine injection were monitored (late withdrawal). At early withdrawal, no significant sensitization occurred for horizontal activity, but cross-sensitization was demonstrated for vertical activity. At late withdrawal, sham controls showed a stress-induced elevation in horizontal activity, with only a trend toward increased vertical activity. Animals given ADX surgery or ADX and CORT 12.5% pellets did not demonstrate sensitization to repeated stress, while CORT 50% pellets in ADX rats restored the sensitized horizontal response to cocaine challenge at late withdrawal. In contrast, stress-pretreated rats which were given CORT 50% pellets during the 2-week withdrawal period after the stress showed a marked decrease in horizontal activity in response to cocaine challenge at late withdrawal. The results provide evidence for a necessary role for adrenal hormones in long term, but not short-term, stress-induced cross-sensitization. Together with our previous study on the role of CORT in cocaine-induced sensitization, the results indicate that CORT is not the common factor mediating the long-term sensitization to cocaine and stress.

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice indicating that rolipram can cause adrenal stimulation in vivo. 6. In summary, these data indicate that systemic production of TNF alpha in response to high dose endotoxin is controlled differently from the local production of TNF alpha in response to low dose endotoxin. The systemic production of TNF alpha is regulated by catecholamines, but not by corticosterone, while the local production of TNF alpha in the peritoneal cavity is not regulated by basal levels of either catecholamines or corticosterone. 7. These data also show that the ability of rolipram to inhibit the local production of TNF alpha is dependent on the release of corticosterone from the adrenal glands.

Effect of exercise and adrenal insufficiency on urea production in rats.

Experiments on Wistar rats were designed to study the effect of exercise on urea production in the liver of intact and adrenalectomized rats. The urea production rate was assessed by the 14C-urea content in liver tissue after administration of NaH14CO3. In intact rats swimming caused increases in 14C-urea content in the liver compared to the resting concentrations in intact control rats: by 45% after 30 min of swimming carrying an additional load of 10% body mass by, 35% after 3 h of swimming without an additional load and by 103% after 10 h of swimming. Concentrations of urea in liver and blood were elevated simultaneously. The specific activity of 14C-urea did not change significantly as a result of the exercise performed. In adrenalectomized rats the basal rate of urea production was reduced by an insignificant amount, but swimming for 3 h resulted in a decrease in liver 14C-urea (by 24%). The results confirmed the exercise-induced increase in urea production and indicated as essential role for adrenal hormones in this response.

Adrenal demedullation blocks and brain norepinephrine depletion potentiates the hyperglycemic response to a variety of stressors

The role of adrenal hormones in mediating the increase in blood glucose levels following several stressful stimuli (environmental and pharmacological) was studied. The role for brain norepinephrine systems in the initiation of the BG response to these challenges was investigated as well. There is disafreement as to whether stress-induced increases in blood glucose levels are mediated primarily by hormonal or neural stimulation of the liver. A stressful stimulus probably causes increases in blood glucose levels by activating neural connections from the brain to both the liver and the adrenal medulla. The relative contribution that each of these pathways makes to the overall blood glucose response may be dependent on certain factors, such as the type of preparation used (awake or anesthetized, fasted or fed) and the intensity of the stimulus used to induce hyperglycemia. In the experiments reported here, which were performed in awaka male rats, we found that increases in blood glucose levels following brief footshock stress, injection of 2-deoxy- d-glucose, exposure to the odor of a predator, and electrical stimulation of the hypothalamus were almost entirely eliminated by removal of the adrenal medullae, a procedure that does not damage hypothalamic norepinephrine systems or the multi-synaptic neural pathways from the hypothalamus to the liver. Furthermore, rather than having impaired blood glucose responses, rats that were depleted of brain norepinephrine showed normal responses to the injection of adrenergic agonists (including epinephrine), and potentiated responses to stressful stimuli compared to non-depleted controls. We conclude that: (1) rapid changes in blood glucose levels that occur following the stressful stimuli used here are mediated mainly by the release of epinephrine from the adrenal medullae and (2) intact brain norepinephrine systems are not required for these increases in blood glucose to occur.

Activation of the adrenal cortex or the peripheral sympatho-adrenomedullary system does not necessarily influence milk ejection in the rat.

Following a 5-h isolation period, primiparous rats have the same milk supply on days 8/9 and 13/14 post partum, yet in response to suckling they release a greater amount of milk at the latter time. Inasmuch as stress is known to inhibit lactation and handling of the pups is stressful to the dams, the question arose as to whether separation from pups before nursing constitutes a greater stress for the dam at the earlier stage of lactation. This possibility was explored in the present study: As an index of stress, changes in plasma corticosterone were measured from chronically cannulated dams. In addition, the role of adrenal hormones and the peripheral sympathetic nervous system in the regulation of milk ejection under these experimental conditions was assessed following bilateral adrenalectomy and treatment with pentolinium, a ganglionic blocker which does not cross the blood-brain barrier. Corticosterone pellets were implanted subcutaneously following adrenalectomy in order to maintain proper lactation. From the results obtained, lactators demonstrated a greater increase in plasma adrenocorticosteroid levels in response to nursing on day 8/9 than on day 13/14 post partum, but milk yield was significantly less at the earlier than at the later stage of lactation. Adrenalectomy in conjunction with corticosterone replacement pellets did not alter milk supply or milk release. The subsequent treatment with pentolinium did not affect milk ejection. Pups still ingested less milk on day 9 than on day 13/14. It is suggested here that the isolation/suckling condition imposed on lactators may be more stressful earlier in lactation. Inasmuch as removal of the adrenal hormones along with ganglionic blockade did not modify the amount of milk ingested by the pups, it is concluded that the smaller milk release observed on day 9 post partum does not result from a direct suppression by the adrenal hormones or by the peripheral sympathetic nervous system on milk ejection.

Corticosteroid receptor plasticity and recovery of a deficient hippocampus-associated behavior after unilateral (dorsal) hippocampectomy

Unilateral ablation of the right dorsal hippocampus (HCX) produced changes in maximal corticosteroid binding capacity (B max) in the contralateral hippocampal lobe of the rat with time. The mechanism by which this time course of changes was produced seemed to involve the pituitary-adrenal system, since a certain difference in corticosteroid receptor binding pattern was noted between chronic adrenalectomized (ADX) rats and rats which remained intact during postlesion survival. In the presence of endogenous adrenal hormones the HCX-induced changes in corticosteroid receptor binding relative to that observed in rats with the overlying neocortex ablated (control) were the following: (1) a 26% decrease at 5 days after HCX; (2) an increase the following 3 weeks with a maximum of 46% at 20 days postsurgery; and (3) recovery towards control values after longer survival times. After discrimination of corticosteroid binding into two corticosterone (CORT) binding receptor populations, e.g. glucocorticoid receptors (GR) and mineralocorticoid-like or CORT receptors (CR), the lesion-induced effect was more pronounced in GR than in CR. A 72% increase over controls was measured at 20 days postsurgery. In the absence of the adrenals, however, the B max of corticosteroid binding was not decreased at 5 days after HCX. The relative increase in B max reached a maximum of 39% over control levels at 30 days postsurgery and recovery towards control values after longer survival did not occur. The increase in corticosteroid receptor capacity after HCX, therefore, is transient in the presence of adrenocortical secretion and permanent in its absence. An attempt was made to relate the changes in corticosteroid receptor capacity to deficits in reversal learning behavior, since it is known that this type of behavior is associated with hippocampus function. Reversal learning behavior in a T-shaped maze was disturbed the first 2 weeks after HCX, but restored the following week. ADX seemed to facilitate recovery of the lesion-induced deficit. Bilateral removal of the hippocampus led to a more permanent deficiency in reversal learning behavior. It is concluded that: (1) unilateral HCX induces a period of considerable plasticity in corticosteroid receptors in particular of the GR type; (2) this receptor plasticity coincides with the recovery of a lesion-induced deficit in hippocampus-associated behavior; and (3) a role of adrenal hormones in regulation of neuronal and corticosteroid receptor plasticity cannot be excluded.

Role of adrenal hormones (adrenaline and DOCA) in experimental hypertension. A histopathological study.

The effect of prolonged treatment with adrenaline and sodium chloride combined with desoxycorticosterone acetate (DOCA), on the blood pressure of unilaterally nephrectomized (UN) rats and the histology of circulatory organs was studied. Hypertension developed in this experimental hypertension model in all of the test groups. Adrenaline alone raised the blood pressure as much as the adrenaline + NaCl + DOCA treatment. Organic changes in the renal blood vessels developed only in the Adrenaline + DOCA + NaCl group, where the highest increases in cardiac and renal organ weights were also found. These findings indicate that adrenal stress hormones may play an important sensitizating role in the multifactoral genesis of vascular changes associated with hypertension.

Role of adrenal hormones and prostaglandins in the control of mouse thymocytes lysis

The cytolytic actions of glucocorticoids and of agents increasing cyclic AMP were studied in vitro in thymocyte suspensions isolated from adrenalectomized or hydrocortisone-treated mice. Although considered as corticoresistant cells, the thymocytes isolated from hydrocortisone-treated mice were lysed to the same extent although more slowly in vitro by dexamethasone than whole thymocyte populations (i.e. corticosensitive cells). Moreover, these two cell populations were shown to contain comparable amounts of glucocorticoid receptors and to be almost equally sensitive to the metabolic effects of glucocorticoids when measured by inhibition of RNA and DNA synthesis. Studies performed with corticosensitive cells showed that prostaglandin E 2, isoproterenol and dibutyrilcyclic AMP were also able to induce cell lysis and that, isoproterenol and dexamethasone exerted additive cytolytic action in vitro. In vivo experiments showed also an additive effect of steroids and isoproterenol on thymus atrophy. In contrast, cells isolated from hydrocortisone-treated animals were not sensitive to the cytotoxic action of prostaglandin E 2, isoproterenol and dibutyril cyclic AMP. This difference between the two populations was not associated with any difference in the responsiveness of adenylate cyclase as determined following isoproterenol-induced accumulation of cyclic AMP. The cytolytic action of dexamethasone but also that of prostaglandin E 2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis. Among the hypotheses proposed to explain the differences between in vitro and in vivo sensitivity of lymphoid cell to glucocorticoids, it was suggested that the drug may in vivo indirectly control the viability or the proliferation of thymocytes through the release of other mediators. We have shown that in vivo injection of hydrocortisone induces an accumulation of fatty acids in the whole thymus gland but not in the isolated thymocytes. Since exogenous fatty acids exert cytolytic actions on isolated thymocytes, we suggest that glucocorticoids may exert in vivo an indirect toxic action by promoting the release of fatty acids from adipose tissue or other sources.

Negligible role of adrenal hormones in regulation of DNA synthesis in livers of partially hepatectomized rats.

SummaryRats were depleted of adrenal corticosteroids by adrenalectomy and orchidectomy, as evidenced by determination of blood levels 1 week later, and by failure of the animals to survive without supplementary NaCl. When 7-day adrenalectomized-orchi-dectomized rats were partially hepatectomized, incorporation of [3H]thymidine into hepatic DNA, indicative of rate of liver regeneration, differed insignificantly from the rate in similarly treated controls, and diverged at only one time point (30 hr) from the rate in regenerating livers of normal rats. The divergence was due to the saline-dextrose injections, not to adrenalectomy-orchidectomy. Administration of adrenal cortical hormones in near physiologic doses did not alter [3H]thymidine incorporation in experimental or control rats. The evidence does not support an important role for these hormones as physiologic regulators of liver growth during hepatic regeneration.

Role of adrenal hormones in incubation behavior of male ring doves (Streptopelia risoria).

Role of adrenal hormones in incubation behavior of male ring doves (Streptopelia risoria).