Distinct characteristics of resistance to Borrelia burgdorferi-induced arthritis in C57BL/6N mice

The diazepam-binding inhibitor (DBI) is a 10-kDa highly evolutionarily conserved multifunctional protein. In mammals, one of DBI's functions is in the activation of steroid hormone biosynthesis via binding to a specific outer mitochondrial membrane receptor (benzodiazepine receptor, BZD) and promoting cholesterol transport to the inner membrane. In this work, a multitiered approach was utilized to study the role of this receptor-like activity in ecdysteroidogenesis by larval insect prothoracic glands (PGs). First, both DBI protein and messenger RNA (mRNA) levels were correlated with peak PG ecdysteroid production. In vitro ecdysteroid production was stimulated by the diazepam analogue FGIN 1-27 and inhibited anti-DBI antibodies. The DBI protein was found distributed throughout PG cells, including regions of dense mitochondria, supposed subcellular sites of ecdysteroid synthesis. Finally, a potential mitochondrial BZD receptor in PG cells was demonstrated by photoaffinity labeling. These results suggest an important role for the insect DBI in the stimulation of steroidogenesis by prothoracic glands and indicate that a pathway for cholesterol mobilization leading to the production of steroid hormones appears to be conserved between arthropods and mammals.     

Enhanced neuroendocrine response to insulin tolerance test performed under increased ambient temperature

The hypothesis that an increase in ambient temperature modulates neuroendocrine response in clinically used provocative pituitary function tests was verified. Healthy male volunteers were subjected to insulin tolerance tests in two randomized trials. In the first trial hypoglycemia was induced by a bolus injection of insulin (0.1 U per kg of BW, i.v.) at room temperature. In the second trial, the subjects were exposed to increased ambient temperature for 45 min before insulin injection and for 45 min thereafter. The environmental temperature was selected to increase body temperature less than 1C. Under conditions of increased temperature basal hormone levels as measured in antecubital venous blood samples failed to be modified and the hypoglycemia was less severe. Nevertheless, the responses of most (beta-endorphin, ACTH, prolactin, catecholamines), but not all (growth hormone, cortisol), hormones to hypoglycemia were exaggerated. The remarkable increase in ACTH and beta-endorphin release was not accompanied by concomitant increase of plasma cortisol response. The sympathetic-adrenomedullary system was significantly activated, which was manifested particularly by enhanced norepinephrine release. Growth hormone response to hypoglycemia was not modified, while that of prolactin was enhanced. Thus during evaluation of neuroendocrine function under clinical conditions, changes in ambient and body temperature should not be underestimated.     

Hormonal markers of stress in acute cerebrovascular pathology

Various studies carried out over the last decade have shown that high glucose levels in the blood foster ischaemic brain damage associated with a worse evolution of such pathologies. The aim of the study we performed was to try to shed some light on whether stress in these patients raised their glucose levels adding to a worsening of the patient's clinical picture. We studied 318 consecutive patients suffering from stroke. We determined fasting glucose levels, prolactin and cortisol within the first few hours of hospitalization and afterwards at seven to ten days and again at one month after the stroke. Clinical severity was evaluated using Toronto and Mathew neurological scales and the degree of incapacity was measured using the Barthel functional scale on the three aforementioned occasions and Rankin's modified scale six and twelve months after the stroke. Clinical severity the first hours after stroke was significantly related to glucose levels, such relationship not being observed with prolactin and cortisol. Nor did we observe any significant association between glucose and these hormones. Likewise the anxiety scale had no relationship with any hormone. Studying medium and long term functional incapacity, glucose significantly correlated with the Rankin scale although with low dependence, such a relationship not being found either with prolactin or cortisol. Our work would seem to indicate that blood glucose behaviour is independent of prolactin and cortisol levels since we found no such relationship between them.     

Influence of inhibitors of prostaglandin synthesis on venoconstrictor responses to bradykinin

The interrelationship between prostaglandins (PGs) and bradykinin (BK) was studied in isolated canine saphenous veins. The hypothesis that PGs mediate the venoconstrictor effect of bradykinin was evaluated by determining the influence of low concentrations of indomethacin (Indo) (1 muM) or eicosa-5,8,11,14-tetraynoic acid (ETA) (3 muM), two inhibitors of PG synthesis, on cumulative concentration-response curves for BK or norepinephrine (NE). In the tissue bath, responses to BK improved with time while responses to NE did not vary. When strips were least responsive to BK, Indo and ETA enhanced these responses. When strips were most responsive to BK, neither inhibitor enhanced the responses. Neither Indo nor ETA altered responses to NE. Phentolamine (10(-8) M) did not alter responses to BK. These data suggest that endogenous PGs act to attenuate, rather than mediate, the venoconstrictor response to BK. Progressive enhancement of responses to BK of untreated saphenous vein strips is associated with a decreased ability of inhibitors of PG synthesis to enhance those responses also. Thus, there may be a time-related decrease in the ability of this preparation to synthesize PGs. From the present results, it cannot be determined whether saphenous veins in vivo are highly responsive or relatively unresponsive to the peptide. However, these data do suggest that PGs are a determinant of venous responsiveness to BK.     

Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice

Stress has been implicated in both somatic and mental disorders. The mechanisms by which stress leads to poor health are largely unknown. However, studies in animals suggest that chronic stress causes high basal cortisol and low cortisol response to acute stressors and that such changes may contribute to disease. Previous studies of the Transcendental Meditation (TM) technique as a possible means of countering effects of stress have reported altered levels of several hormones both during the practice and longitudinally after regular practice of this technique. In this prospective, random assignment study, changes in baseline levels and acute responses to laboratory stressors were examined for four hormones-cortisol, growth hormone, thyroid-stimulating hormone and testosterone-before and after 4 months of either the TM technique or a stress education control condition. At pre- and post-test, blood was withdrawn continuously through an indwelling catheter, and plasma or serum samples were frozen for later analysis by radioimmunoassay. The results showed significantly different changes for the two groups, or trends toward significance, for each hormone over the 4 months. In the TM group, but not in the controls, basal cortisol level and average cortisol across the stress session decreased from pre- to post-test. Cortisol responsiveness to stressors, however, increased in the TM group compared to controls. The baselines and/or stress responsiveness for TSH and GH changed in opposite directions for the groups, as did the testosterone baseline. Overall, the cortisol and testosterone results appear to support previous data suggesting that repeated practice of the TM technique reverses effects of chronic stress significant for health. The observed group difference in the change of GH regulation may derive from the cortisol differences, while the TSH results are not related easily to earlier findings on the effects of chronic stress.     

Effects of hormones on protein and amino acid metabolism in mammary-gland explants of mice

The effects of insulin, cortisol and prolactin on amino acid uptake and protein biosynthesis were determined in mammary-gland explants from mid-pregnant mice. Insulin stimulated [3H]leucine incorporation into protein within 15 min of adding insulin to the incubation medium. Insulin also had a rapid stimulatory effect on the rate of aminoiso[14C]butyric acid uptake, but it had no effect on the intracellular accumulation of [3H]leucine. Cortisol inhibited the rate of [3H]leucine incorporation into protein during the initial 4h of incubation, but it had no effect at subsequent times. [3H]Leucine uptake was unaffected by cortisol, but amino[14C]isobutyric acid uptake was inhibited after a 4h exposure period to this hormone. Prolactin stimulated the rate of [3H]leucine incorporation into protein when tissues were exposed to this hormone for 4h or more; up to 4h, however, no effect of prolactin was detected. At all times tested, prolactin had no effect on the uptake of either amino[14C]isobutyric acid or [3H]leucine. Incubation with actinomycin D abolished the prolactin stimulation of protein biosynthesis, but this antibiotic did not affect the insulin response. A distinct difference in the mechanism of action of these hormones on protein biosynthesis in the mammary gland is thus apparent.     

Plasma prolactin responses to thyrotropin-releasing hormone in patients with breast cancer

Plasma human prolactin levels were measured by homologous radioimmunoassay in patients with primary breast cancer and in normal women of similar age. In normal controls mean (+/- SEM) basal plasma prolactin levels were 11.9 +/- 1.5 ng/ml and intravenous injection of synthetic thyrotropin-releasing hormone (TRH), 500 mug, caused a significant rise in plasma prolactin in all subjects examined with a maximum response of 52.6 +/- 3.3 ng/ml (mean +/- SEM). Markedly high plasma prolactin levels and exaggerated plasma prolactin responses to TRH were demonstrated in some patients with breast cancer. However, mean basal plasma prolactin levels and mean plasma prolactin increments following TRH in patients with breast cancer did not differ significantly from those in normal subjects. Plasma prolactin responses to TRH were slightly blunted during the administration of androgen in patients with breast cancer. These results suggest that some of the patients with primary breast cancer have abnormal prolactin secretion.     

Individual differences in freezing and cortisol in infant and mother rhesus monkeys

Freezing is an adaptive defensive behavior that is expressed in response to an imminent threat. In prior studies with rhesus monkeys, stable individual differences in animals' propensities to freeze have been demonstrated. To understand the factors associated with these individual differences, freezing behavior was examined in infant rhesus monkeys and their mothers, in conjunction with levels of the stress-related hormone cortisol. In both mothers and infants, basal cortisol levels were positively correlated with freezing duration. Additionally, the number of offspring a mother had was negatively correlated with her infant's cortisol level. These findings suggest a link between basal cortisol levels and an animal's propensity to freeze, as well as a mechanism by which maternal experience may affect infants' cortisol levels.     

Hormonal changes and pituitary histological and immunocytochemical studies of patients with multiple organ failure

OBJECTIVE: We investigated the correlation between the endogenous hormonal changes of pituitary-adrenal and pituitary-thyroid hormones and the prognosis of patients in multiple organ failure, and elucidated the mechanism of blunted thyrotropin (TSH) secretion by histological and immunocytochemical studies of anterior pituitary glands. PATIENTS: Forty-three patients were studied who had been admitted to the intensive care unit of Sapporo Medical University Hospital and had been diagnosed as having multiple organ failure. MEASUREMENTS: Pituitary adrenal hormones [corticotropin (ACTH), cortisol] and pituitary thyroid hormones [TSH, triiodothyronin (T3), free-T3, thyroxine (T4), free-T4, thyroxine-binding globulin (TBG)] were measured, and TSH and prolactin (PRL) responses thyrotropin-releasing hormone (TRH) were examined within 24 hours of admission to the ICU. Individual variables were compared between survivors (n = 19) and nonsurvivors (n = 24). Thirteen patients (five survivors, eight nonsurvivors) were investigated again before discharge from the ICU or death. Morphology was examined by hematoxilin-eosin staining, and avidin-biotin-peroxidase complex immunostaining was used to demonstrate the spectrum of TSH in 14 nonsurvivors. RESULTS: (1) ACTH levels remained within the normal range, while cortisol levels increased to above normal levels. Neither hormone showed significant differences between survivors and nonsurvivors. In nonsurvivors, cortisol levels decreased before death despite the increased ACTH levels. (2) T3 and free-T3 levels decreased markedly to below normal values, and reverse-T3 levels increased markedly to above normal values. Nonsurvivors showed significant differences in TSH, T4 and reverse-T3 levels compared with survivors. (3) TSH response to TRH was blunted in both groups but PRL response to TRH was normal. Nonsurvivors showed severely depressed TSH response. Nonsurvivors continued to show blunted TSH response to TRH, while this improved in survivors. (4) The histological study did not show very serious damages to anterior pituitary glands as TSH secretion was depressed. Many TSH immunoreactive cells were also observed by immunocytochemical study. CONCLUSION: Decreased cortisol, low T4 levels and blunted TSH response to TRH correlated with mortality in MOF patients. Histological and immunocytological studies suggest that blunted TSH secretion is not caused by pituitary damages or TSH exhaustion but by disturbances in TSH secretion. This blunted TSH secretion is reversible and its improvement is an indicator of survival.     

Increased testosterone-to-cortisol ratio in psychopathy.

Only a few studies have examined hormones in psychopathy, and results have been mixed. It has been suggested that because hormone systems are highly interconnected, it may be important to examine multiple systems simultaneously to gain a clearer picture of how hormones work together to predispose for a certain construct. In the present study, we attempt to clarify the role of the hormones cortisol and testosterone in psychopathy by examining both hormones in a community sample of 178 adults demonstrating a wide range of psychopathy scores. Results showed that psychopathy scores were associated with an increased ratio of testosterone (baseline) to cortisol responsivity to a stressor. Psychopathy was not associated with either of these measures independently or with baseline cortisol levels. These findings suggest that these highly interconnected hormone systems may work in concert to predispose to psychopathy. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Pergolide, a potent long-acting dopamine-receptor agonist

After single doses (100 to 400 microgram orally), pergolide, a synthetic ergot, reduced basal plasma prolactin levels in normal subjects in a dose-related manner. This effect persisted for more than 24 hr. Multiple doses of pergolide (150 to 250 microgram daily for 7 days) resulted in a plasma prolactin decrease of more than 80%. A single dose of pergolide (150 microgram orally) suppressed plasma prolactin and abolished the plasma prolactin diurnal rhythm, i.e., suppression of sleep-induced elevation in plasma prolactin during a 40-hr period. Perphenazine (5 mg intramuscularly)-induced plasma prolactin elevation was inhibited by pergolide; the effect was dose dependent. After single or multiple doses, pergolide had no effect on plasma follicle-stimulating hormone, luteinizing hormone, cortisol, growth hormone, and thyroid-stimulating hormone. Pergolide appears to have specificity at the pituitary level for the dopamine receptors that mediate prolactin secretion.     

Hypofunction of the stress axis in Sj?gren's syndrome

OBJECTIVE: To examine the functional integrity of the hypothalamic-pituitary-adrenal (HPA) and thyroid axes in Sj?gren's syndrome (SS) via the assessment of basal and stimulated adrenocorticotropin (ACTH), cortisol, thyroid stimulating hormone (TSH), and prolactin levels. METHODS: Pituitary function of the HPA axis was assessed by determining the basal plasma levels of ACTH in the late afternoon, as well as the ACTH released to ovine corticotropin releasing hormone (oCRH) stimulation; adrenal function was assessed by measuring plasma cortisol levels in the late afternoon at baseline and after release of the endogenous ACTH during oCRH stimulation. Basal and thyrotropin releasing hormone (TRH) stimulated levels of TSH and prolactin were also assessed. Healthy volunteers were used as controls. RESULTS: Patients with SS, compared to controls, were characterized by significantly lower ACTH levels (pg/ml), (5.1 +/- 0.5 vs 11.4 +/- 1.5, respectively; p < 0.05) and cortisol levels (microg/ml), (2.4 +/- 0.6 vs 5.9 +/- 1.2, respectively; p < 0.05). Furthermore, a blunted pituitary and adrenal response to oCRH compared to controls was observed: peak plasma ACTH and cortisol levels for patients with SS were 46.2 +/- 5.4 pg/ml and 15.7 +/- 1.6 microg/ml, respectively, and for controls 61.5 +/- 3.8 and 19.6 +/- 0.7, respectively (p < 0.05). Basal TSH levels were significantly elevated in patients (1.3 +/- 0.3 microIU/ml vs 0.9 +/- 0.05 microIU/ml; p < 0.05). CONCLUSION: The above findings indicate hypoactivity of the HPA axis in patients with SS. Further studies are needed to definitively identify the locus of the defects and assess the significance of the pattern of the perturbations to the pathogenesis and expression of SS.     

Effects of environmental and other stressors on blood hormone patterns in lactating animals

Recent data on various environmental stressors and blood hormone patterns are presented for lactating cattle. Known stressor effects of such factors as environmental temperature, air pollution, and noise on the plasma thyroxine, growth hormone, cortisol, prolactin, progesterone, luteinzing hormone, epinephrine, and norepinephrine of lactating cattle are discussed. Information on stressor effects is lacking on glucagon, insulin, vasopressin, calcitonin, oxytocin, thyrotrophic hormone, follicle stimulating hormone, melatonin, parathyroid hormone, and estrogens in the lactating cow. The importance of evaluating both the effect of environmental stressor and of production or lactation intensity is emphasized in the overall interpretation of changes in hormone of plasma. The short and long term environmental heat effects on thyroxine, cortisol, and growth hormone are clear with initial increased due to acute stressors and a decline of amounts in plasma after prolonged exposure to stressors. The relationship of amounts in plasma of these hormones to milk production appears to be related directly for cortisol, growth hormone, and prolactin with an inverse relationship with thyroxine. Epinephrine and norepinephrine seem to be elevated with prolonged environmental heat stress. However, the influence of intensity of lactation has not been measured. Hormones in plasma as they relate to stressor effects and milk production are important as potential indicators of the physiological state of a cow and reflect the physiological compensations a cow undergoes at various lactation intensities and/or stress exposure.     

Studies on the mechanism by which thyroid hormones enhance alpha-lactalbumin activity in explants from mouse mammary glands

Addition of 3,5,3'-triiodo-L-thyronine to cultures of mammary gland explants in serumfree medium containing insulin, hydrocortisone and prolactin results in a 3 to 5-fold increase in the activity of the milk-protein alpha-lactalbumin over that seen in the presence of the latter three hormones alone. The thyroid hormone does not act by substituting for any of the other hormones. It need not be present throughout the culture period but can act if added along with prolactin after insulin and hydrocortisone have induced formation of the rough endoplasmic reticulum. Delayed addition of the thyroid hormone also results in further stimulation of cells already responding maximally to insulin, hydrocortisone and prolactin. These effects of triiodothyronine are not blocked by progesterone at 1 microng per ml. They are, however, blocked by the addition of inhibitors of RNA (actinomycin D) or protein (cycloheximide or puromycin) synthesis, suggesting that the thyroid hormone increases the synthesis of the alpha-lactalbumin molecule itself. The thyroid hormone appears to act by altering the responsiveness of the mammary gland explants to prolactin, but not to insulin or hydrocortisone. In the presence of 10-9M triiodothyronine, enhanced alpha-lactalbumin activity is consistently obtained at prolactin concentrations as low as 4.5 x 10(-12)M whereas, in the absence of the thyroid hormone, ten times more prolactin (4.5 x 10(-11)M) is needed to obtain an increase in alpha-lactalbumin activity.     

Marital conflict and endocrine function: Are men really more physiologically affected than women?

This study assessed marital conflict behavior and endocrine function in 90 newlywed couples. Blood samples acquired hourly from 8:00 a.m. through 10:00 p.m. were combined to provide composite daytime values for 3 stress hormones--epinephrine ( EPI ), norepinephrine ( NEPI ), and cortisol -- and 3 related hormones (ACTH, growth hormone, and prolactin). These pooled data provided a window on endocrine function in couples for whom the day included a conflict. For wives, higher probabilities of husband's withdrawal in response to wife's negative behavior were associated with higher NEPI and cortisol levels. In addition, higher frequencies of positive behaviors were associated with lower EPI and higher prolactin levels among wives. Husbands' endocrine data were not associated with behavioral data. These findings are discussed in the context of gender models of marital conflict. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypothalamic dopamine D1 receptors are involved in the stimulation of prolactin secretion by high environmental temperature in the female sheep

Recent evidence suggests that dopamine, acting via its D1 receptors, may function as a neurotransmitter in intrahypothalamic pathways involved in the stimulation of prolactin secretion. Functional dopamine D1 receptors are present in the ventromedial hypothalamic nucleus (VMH) and we hypothesized that they might be part of a prolactin-stimulatory pathway activated by stress. We tested this hypothesis in a series of experiments on sheep involving two different forms of stressors, audiovisual (barking dog) and high environmental temperature. We attempted to block the stimulation of prolactin secretion by infusion into the VMH of an antagonist specific for the D1 receptor. Ovariectomised, oestradiol-implanted merino ewes were surgically implanted with bilateral guide tubes directed at the VMH. After a 180 min pretreatment period, the ewes either were or were not exposed to a stressor (30 min of barking dog or 120 min at 35 degrees C, 65% relative humidity). D1 receptor antagonist, SCH23390 or vehicle (0.9% saline) was infused into the VMH (1.7 microliters/h, 120 nmol/h) for 60 min prior to and during the stressor period. Blood was sampled every 15 min via jugular cannulae and the plasma was assayed for prolactin, cortisol and growth hormone (GH). Both stressors significantly increased prolactin concentrations over control levels. SCH23390 infusion significantly attenuated the prolactin response to high environmental temperature, but had no effect on the prolactin response to audiovisual stress. Cortisol concentrations were significantly increased by audiovisual stress only and were not affected by SCH23390. GH concentrations were not changed by either stressor or infusion. Drug infusion alone did not affect the concentration of the hormones. The data suggest that the VMH D1 receptors are involved in a prolactin stimulatory pathway in response to high environmental temperature. The inability of the D1 antagonist to affect the response to the barking dog indicates that this pathway is stress-specific, implying that there is more than one mechanism or pathway involved in the prolactin response to different stressors.     

Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication

PURPOSE: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone-binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs. METHODS: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17alpha-hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin-like growth factor-I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid-stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men. RESULTS: In the female patients, TSH, DHEAS, follicular-phase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17alpha-hydroxyprogesterone, free testosterone, inhibin B, and the testosterone/LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone/LH ratio in 50% indicates an impaired Leydig's cell function. CONCLUSIONS: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17alpha-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.     

Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs

Pituitary function was assessed in healthy adult beagle dogs before and after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consisted of sequential 30-sec intravenous injections of four hypothalamic releasing hormones, in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanotropin (alpha-MSH) response to the intravenous injection of the dopamine antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyroxine, LH. PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test and the haloperidol test, the peaks for the plasma concentrations of ACTH, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after injection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol responses, whereas in the other four dogs, plasma ACTH and cortisol responses were significantly attenuated. The basal plasma ACTH and cortisol concentrations were significantly lower in the corticotropic nonresponders than in the responders. Plasma AVP responses were completely abolished by hypophysectomy, although water intake by the dogs was normal. Histopathological examinations at 10 wk after hypophysectomy revealed that adrenocortical atrophy was much more pronounced in the corticotropic nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon. However, in all hypophysectomized dogs that were investigated, islets of pituitary cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH-immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anterior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the anterior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysiotropic stimulation are the most sensitive indicators for residual pituitary function after hypophysectomy, 4) small islets of pituitary cells in the sella turcica, containing corticotropic cells, are the most likely source of the attenuated corticotropic response that may occur after hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, despite the fact that the AVP response to hypertonic saline infusion is completely abolished.     

Circadian responsiveness of the hypothalamic-pituitary axis

Five healthy men 25-38 years old were subjected to simultaneous composite intravenous stimulation tests of insulin hypoglycemia (0.1 U/kg), thyrotropin-releasing hormone (TRH, 100 mug), and luteinizing hormone-releasing hormone (LHRH, 50 mug) at weekly intervals to study the circadian responsiveness of the hypothalamic-adenohypophyseal axis at 0600, 1200, 1800, and 0000 hours. Blood sugar (BS), LH, follicle-stimulating hormone, TSH, prolactin, cortisol (C), growth hormone, and testosterone (T) levels were estimated before and after the administration of drugs. Comparisons were made between basal and delta values (difference between basal and peak or nadir levels) at different tests. Significant circadian variations in BS, GH, C, and, to a lesser extent PRL, responses were observed 0600 h basal and delta BS values were the lowest, delta BS was highest at 0000 h accompanied by maximal hypoglycemic symptoms; the delta values of both C and GH were significantly higher at 0600 h and 0000 h; highest mean delta PRL was observed at 0600; at 1800 h the basal plasma PRL level was maximum but the delta PRL was lowest. Plasma TSH, LH, and FSH responses did not show significant circadian variations. These results suggest that circadian variations are evident when stimuli act through central or hypothalamic mechanisms; however, direct stimulation of the adenohypophysis resulted in indentical responses at different periods tested.     

Calcitropic peptides: neural perspectives

In mammals and higher vertebrates, calcitropic peptides are produced by peripheral endocrine glands: the parathyroid gland (PTH), thyroid or ultimobranchial gland (calcitonin) and the anterior pituitary gland (growth hormone and prolactin). These hormones are, however, also found in the neural tissues of lower vertebrates and invertebrates that lack these endocrine organs, suggesting that neural tissue may be an ancestral site of calcitropic peptide synthesis. Indeed, the demonstration of CNS receptors for these calcitropic peptides and their induction of neurological actions suggest that these hormones arose as neuropeptides. Neural and neuroendocrine roles of some of these calcitropic hormones (calcitonin and parathyroid hormone) and related peptides (calcitonin gene related peptide, stanniocalcin and parathyroid hormone related peptide) are thus the focus of this review.