PubMed Health⌕ Search

Biomedical subjects

H Watanobe

Publications and source records attributed to H Watanobe.

At least 55 records · Page 3Linked to original sources
PubMed1997

A suppressive effect of dexamethasone (DEX) on adrenocorticotropin (ACTH) response to vasoactive intestinal peptide (VIP) in Cushing's disease: a parallel modulation by DEX of ACTH responses to VIP and corticotropin-releasing hormone.

We have previously reported and confirmed that vasoactive intestinal peptide (VIP) is a significant stimulator of ACTH and cortisol secretion in at least some patients with Cushing's disease. We have also found that the hormonal responses to corticotropin-releasing hormone (CRH) in VIP-responsive patients with Cushing's disease were higher than those in VIP non-responders, which suggested a linkage between the actions of CRH and VIP in this disorder. Therefore, in the present study we examined whether this linkage also exists after glucocorticoid treatment by testing the effect of dexamethasone (DEX) pretreatment (1.0 mg, intravenous bolus, 60 min before) on ACTH and cortisol responses to CRH (100 microg, i.v. bolus) and VIP (100 microg, i.v. bolus) in 7 patients with Cushing's disease who were responsive to both neuropeptides while under no DEX pretreatment. The results were that in 5 patients, DEX was able to significantly suppress the ACTH and cortisol responses to both CRH and VIP, and in the remaining 2 patients, DEX did not significantly affect the action of either CRH or VIP. This study is the first to demonstrate the parallel inhibition by DEX of ACTH and cortisol responses to CRH and VIP in Cushing's disease. Although the possibility cannot be excluded that VIP may act on CRH receptors in corticotropinomas as a partial agonist, it seems more likely that specific receptors for CRH and VIP, respectively, may concurrently express in substantial quantity in those corticotropinomas that are responsive to both neuropeptides.

Adrenocorticotropic Hormone↗
PubMed1997

A comparative study of adrenocorticotropin-releasing activity of prostaglandins E1, E2, F2 alpha and D2 in the rat.

There is substantial evidence to indicate that prostaglandin (PG) E2 exerts a stimulatory effect on the hypothalamo-pituitary-adrenal axis in rodents. However, little is known regarding the possibility that other PGs play a similar role in regulating the endocrine axis. Therefore, in this study we compared the effects of intravenous administration of PGs E1, E2, F2 alpha and D2 on adrenocorticotropin (ACTH) secretion in conscious male rats. Each PG was administered at two doses of 0.1 and 1.0 mg/kg body weight, and blood samples were collected sequentially up to 120 min postinjection. Although PGD2 was without effect on ACTH secretion at either dose, PGs E1, E2 and F2 alpha all significantly stimulated the hormonal response at both doses. Interestingly, PGs E1, E2 and F2 alpha were largely equipotent in stimulating ACTH release. To the best of our knowledge, this is the first study to demonstrate significant ACTH-releasing activity of intravenously administered PGs E1 and F2 alpha in the rat. These results suggest that PGE2 might not be the only prostanoid playing a role in regulating the hypothalamo-pituitary-adrenal axis and, thus, multiple PGs may be involved in the endocrine axis.

Adrenocorticotropic Hormone↗
PubMed1996

Stimulation by neuropeptide Y of growth hormone secretion in prolactinoma in vivo.

We examined the effects of intravenous bolus injection of human neuropeptide Y (NPY, 100 micrograms) on the plasma growth hormone (GH) and prolactin (PRL) responses in 15 patients with prolactinoma (PRLoma). The GH and PRL responses to NPY were considered positive (a paradoxical increase) when an increase over baseline of at least 100% occurred. Although NPY did not affect PRL secretion in any of the patients examined, 60% (9 of 15) of the patients showed a significant rise in GH secretion after NPY. The presence or absence of the positive paradoxical increase in GH after NPY was not related to the age of the patients, basal PRL levels, the size of the pituitary adenoma (macro- or microadenoma), or the presence or absence of suprasellar extension of the adenoma. Although the underlying mechanism of the NPY stimulation of GH secretion and also its pathophysiological significance in PRLoma are open to question, the present observation may represent another example of paradoxical hormone responses which are occasionally found in functioning pituitary adenomas.

Adolescent↗
PubMed1995

Role of prostaglandins E1, E2 and F2 alpha in the brain in interleukin 1 beta-induced adrenocorticotropin secretion in the rat.

It is well known that interleukin (IL)-1 is a potent activator of the hypothalamo-pituitary-adrenal axis in the rat. Many studies have reported that prostaglandins (PGs), especially PGE2, in the brain may mediate the IL-1 stimulation of corticotropin-releasing hormone release, which then leads to adrenocorticotropin (ACTH) secretion. However, a general consensus has yet to emerge regarding whether PGE2 is the only or the most important PG in the brain mediating IL-1-induced ACTH secretion in the rat. To address this question, we examined the effect of intracerebroventricular (icv) administration of antisera against PGE1, PGE2 or PGF2 alpha, or normal rabbit serum on the ACTH response induced by an icv injection of IL-1 beta in the rat. Each antibody or normal rabbit serum (as the control) was given icv 15 min before an icv administration of human recombinant IL-1 beta (50 ng). IL-1 beta produced a significant rise in plasma ACTH levels, and this response was significantly suppressed by either of the three PG antibodies. Interestingly, the inhibitory effect of anti-PGE2 antibody seemed to be somewhat weaker than those of the other two antibodies. We conclude that not only PGE2 but also PGE1 and PGF2 alpha in the brain may mediate the IL-1 beta stimulation of ACTH secretion in the rat.

Adrenocorticotropic Hormone↗
PubMed1995

A re-evaluation of the prolactin-releasing activity of growth hormone-releasing hormone in acromegaly in vivo.

In 1985, Losa et al reported that an i.v. bolus injection of GH-releasing hormone (GHRH) was able to paradoxically stimulate PRL secretion in more than half of their acromegalic patients. However, this observation was not generally accepted since several other investigators have concluded that such an anomalous PRL response to GHRH was an extremely rare phenomenon in acromegaly. Therefore, in this study we examined a large number (51 patients) of active acromegalics in order to obtain more reliable data on the incidence of the paradoxical PRL response to GHRH in this disorder. Each patient underwent i.v. bolus injections of GHRH (100 micrograms) and thyrotropin-releasing hormone (TRH, 500 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma PRL response to GHRH was considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. We found that only 6 patients (12%) showed a positive PRL response to GHRH. These PRL-responders to GHRH had higher GH responses to this peptide than PRL-non-responders to GHRH. Although PRL-responders and non-responders to GHRH had a similar PRL responsiveness to TRH, the GH response to TRH was lower in PRL-responders to GHRH than PRL-non-responders to this peptide. In addition, PRL-non-responders to GHRH had lower basal GH and higher basal PRL levels than PRL-responders to GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1995

Clinical significance of the growth hormone response to vasoactive intestinal peptide and gonadotropin-releasing hormone in acromegaly.

GH-secreting pituitary adenomas causing acromegaly can be classified into at least two types, i.e. the lactotroph-like adenoma and somatotroph-like adenoma. From a functional point of view, the lactotroph-like adenoma is characterized by positive GH responses to TRH and bromocriptine (Br) with a GH increase or decrease, respectively, whereas the somatotroph-like adenoma is characterized by a high GH response to GHRH and a low GH response to TRH and Br. In this study, we examined whether the loading of vasoactive intestinal peptide (VIP) and GnRH, another hypothalamic hormone capable of stimulating GH secretion in acromegaly, have a pathophysiological significance as TRH, GHRH, and Br tests. In 52 patients with active acromegaly, we performed iv bolus injections of TRH (500 micrograms), GHRH (100 micrograms), VIP (100 micrograms), and GnRH (100 micrograms), and a peroral administration of Br (2.5 mg), in order to compare the GH responses to these loads. There was a significant correlation that the higher was the GH response after TRH the greater was the GH decrease after Br. Although statistically insignificant, there was a trend (0.05 < p < 0.1) that the higher was the GH response after GHRH the smaller was the GH decrease after Br. In addition, as novel findings, we observed that the GH responses to GHRH, VIP, and GnRH were in significant positive correlations to each other, and that the higher were the GH responses after VIP and GnRH the smaller was the GH decrease after Br. In agreement with this, we also found that a simultaneous GH responsivity to VIP and/or GnRH in TRH-responsive acromegalics significantly enhanced the GH response to GHRH and lowered the Br responsiveness compared to the data of pure TRH-responders. From these results, we hypothesize that the positive GH responsiveness to VIP and GnRH, like that to GHRH, may be a feature of the somatotroph-like pituitary adenoma causing acromegaly. The present results appear to be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testings in acromegaly.

Acromegaly↗
PubMed1995

Effect of thyroid status on the prolactin-releasing action of vasoactive intestinal peptide in humans: comparison with the action of thyrotropin-releasing hormone.

Recent studies have shown that primary hypothyroidism induced in the rat was able to stimulate the biosynthesis of vasoactive intestinal peptide (VIP) in the anterior pituitary (AP). Since the AP VIP is known to stimulate prolactin (PRL) secretion through a paracrine and/or autocrine mechanism, it is interesting to hypothesize that hyperprolactinemia seen in hypothyroid patients may at least in part be due to a paracrine effect of elevated VIP on AP PRL secretion. Prompted by this information, we in the present study examined the effect of VIP load on PRL secretion in patients with primary hyperthyroidism or hypothyroidism, and compared the data with those from thyrotropin-releasing hormone (TRH) load performed in the same patients. Eight female patients with Graves' disease and 8 females with chronic thyroiditis received intravenous bolus injections of VIP (100 micrograms) and TRH (500 micrograms) 2-3 days apart from each other, during both the dysthyroid and euthyroid (attained by medical treatment) states. Compared to the data in the euthyroid state of the respective group, hyperthyroidism was associated with a lower basal PRL level and a lower PRL responsiveness (estimated by net percent increase in PRL) to TRH, whereas hypothyroidism was associated with higher values of these parameters. With respect to VIP, although the peptide was able to significantly stimulate PRL secretion during both the dysthyroid and euthyroid states of hyper- and hypothyroid patients, PRL responsiveness to VIP was essentially the same regardless of thyroid status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A study on the role of circulating prostaglandin E2 in the adrenocorticotropin response to intravenous administration of interleukin-1beta in the rat.

It is almost generally agreed that prostaglandins (PGs), especially PGE2, may play a significant role in mediating corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) secretion by interleukin (IL)-1. The origin and site of action of PGE2 involved in this response appear to be within the brain, but the possibility has yet to be excluded that circulating PGE2, which increases after a systemic administration of IL-1, enters the brain to stimulate CRH and ACTH release. In this study, we attempted to answer the question utilizing in vivo experimental paradigms in conscious male rats. Intravenous bolus injection of recombinant human IL-1beta (3 mu g/kg) caused a prompt and robust rise in plasma ACTH (peak, 748 +/- 183 (-x +/- SE) pg/ml at 20 min), but this was not associated with a significant change in plasma PGE2 up to 120 min postadministration. Intravenous bolus injection of PGE2 at doses of 0.1 mg and 1.0 mg/kg BW resulted in dose-dependent significant elevations of the plasma ACTH with peak levels being 155 +/- 27 pg/ml (at 10 min) and 343 +/- 35 pg/ml (at 20 min), respectively. Peak PGE2 levels in the plasma which occurred 10 min after injecting either dose of PGE2 were 13,245 +/- 5,093 and 57,150 +/- 350 pg/ml, respectively. Thus the ACTH response which followed the plasma PGE2 levels of 13,000-57,000 pg/ml was even lower than the ACTH response to IL-1beta which did not cause a significant rise in the plasma PGE2. We conclude from these results that circulating PGE2 is not involved in the ACTH response to intravenous administration of IL-1beta. It is thus very likely that the source and site of action of PGE2 mediating the hormonal response are in the brain. However, this study does not exclude a possible role for other circulating PGs in the IL-1beta stimulation of ACTH secretion in the rat.

Adrenocorticotropic Hormone↗
PubMed1995

A case of cyclical Cushing's disease associated with corticosteroid-binding globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease.

We experienced an extremely unusual combination of Cushing's disease and corticosteroid-binding globulin (CBG) deficiency that has been reported in only one similar case to date. A 53-year-old woman presented at a medical clinic with clinical Cushing's disease. However, her plasma levels of adrenocorticotropin (ACTH) and cortisol were in the normal range. Six months later, during a second visit, a high urinary excretion of 17-hydroxycorticosteroids was found, but plasma ACTH and cortisol levels were normal again. Further investigation revealed a decreased CBG concentration. Free plasma cortisol levels were clearly elevated. Furthermore, the Cushing's disease of our patient was complicated by periodic secretion of ACTH and cortisol, with high or normal outputs of corticosteroids occurring alternately every 1-3 days, which explained the occasionally normal plasma ACTH and cortisol levels. A combination of a decreased serum CBG concentration and periodic secretion of ACTH can be an important pitfall in the diagnosis of Cushing's disease.

17-Hydroxycorticosteroids↗
PubMed1994

Neuropeptide Y potentiates the luteinizing hormone (LH) response to LH-releasing hormone in men.

It has been demonstrated in several animal species that neuropeptide Y (NPY) exerts a modulatory effect on luteinizing hormone (LH) secretion. However, whether NPY plays a similar role also in humans has yet to be determined. Therefore, in this study we examined the effect of human NPY on the anterior pituitary hormone secretion in 6 normal men. Intravenous bolus injection of 100 micrograms of human NPY alone did not affect the secretion of any anterior pituitary hormone or cortisol. However, when NPY (100 micrograms) was administered simultaneously with LH-releasing hormone (LHRH, 100 micrograms), a significant potentiation was observed for LHRH-induced LH secretion. Similarly, follicle-stimulating hormone (FSH) response to LHRH was slightly potentiated by the coadministration of NPY, although this effect was not statistically significant. This is the first study to demonstrate that NPY can augment the LHRH-induced LH secretion in humans.

Adult↗
PubMed1994

Lack of involvement of the cholinergic mechanism in vasoactive intestinal peptide- and peptide-histidine methionine-induced growth hormone (GH) responses in acromegaly: comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing hormone.

We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 micrograms), GH-releasing hormone (GHRH, 100 micrograms), VIP (100 micrograms), and PHM (100 micrograms) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 micrograms/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not.

Acetylcholine↗
PubMed1994

Anomalous growth hormone response to vasoactive intestinal peptide and peptide histidine methionine in patients with prolactinoma or hypothalamic hyperprolactinemia.

We examined a possible GH-releasing activity of vasoactive intestinal peptide (VIP) and its homologous peptide, peptide histidine methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 micrograms) and PHM (100 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects of intravenous administration of interleukin-1-beta on the release of prostaglandin E2, corticotropin-releasing factor, and arginine vasopressin in several hypothalamic areas of freely moving rats: estimation by push-pull perfusion.

Utilizing the push-pull perfusion technique, we examined the effect of an intravenous bolus injection of recombinant human interleukin (IL)-1 beta on the release of prostaglandin E2 (PGE2), CRF, and AVP in several hypothalamic areas of freely moving rats, simultaneously monitoring plasma ACTH levels. Perfused hypothalamic areas were the median eminence (ME), the paraventricular nucleus (PVN), and the medial preoptic area (MPOA). During the period 12:00-15:00 h, perfusates and blood samples were collected every 10 min (between 13:00 and 13:40 h) or 20 min (between 12:00 and 13:00 h, and between 13:40 and 15:00 h). IL-1 beta (1.0 micrograms/rat) or vehicle only (in control groups) was injected at 13:00 h. In both the ME and the PVN but not in the MPOA, the outputs of CRF and AVP were significantly stimulated by IL-1 beta, prior to the rise in plasma ACTH. A significant stimulation of PGE2 by IL-1 beta was observed only in the PVN, and its temporal profile was very similar to those of CRF and AVP in the PVN. These results suggest that PGE2 may be a trigger in the PVN for the activation of CRF and AVP neurons, and thereby ACTH secretion, which follows IL-1 beta injection.

Adrenocorticotropic Hormone↗
PubMed1994

Stimulation by peptide histidine methionine (PHM) of adrenocorticotropin secretion in patients with Cushing's disease: a comparison with the effect of vasoactive intestinal peptide (VIP) and a study on the effect of combined administration of corticotropin-releasing hormone with PHM or VIP.

The effect of peptide histidine methionine (PHM) on ACTH and cortisol secretion was examined in 12 female patients with Cushing's disease and 8 normal women. For comparison, we examined in both groups the effects of vasoactive intestinal peptide (VIP), human (h) CRH plus PHM, and hCRH plus VIP. Each peptide was given as an i.v. bolus in a dose of 100 micrograms, and plasma levels of ACTH and cortisol were measured before and at intervals up to 120 min after the injection. In all normal subjects, hCRH induced significant rises in ACTH (> 50% above the basal) and cortisol (> 20% above the basal), but PHM and VIP were without effect. In this group, hormonal responses after hCRH plus PHM and hCRH plus VIP were statistically indistinguishable from those after hCRH alone. Of the patients with Cushing's disease, 9 (75%) were responsive to hCRH, 5 (42%) were to VIP, and 3 (25%) were to PHM, showing significant increases in both ACTH and cortisol. All the 3 PHM responders were also responsive to VIP, and all the 5 VIP responders were also responsive to hCRH. Interestingly, the responders to VIP and PHM had higher ACTH and cortisol responses to hCRH compared with the nonresponders. In addition, in the patients with Cushing's disease the coadministration of hCRH with PHM or VIP produced additive increases in both ACTH and cortisol. These results suggest that PHM may be another hypothalamic hormone capable of paradoxically stimulating ACTH secretion in at least some patients with Cushing's disease. Although the ACTH-releasing action of PHM appears less potent than those of hCRH and VIP, the possibility was suggested that a certain common mechanism may operate in inducing the ACTH response to these 3 peptides.

Adrenocorticotropic Hormone↗
PubMed1993

Contradictory clinical implications between paradoxical growth hormone responses to thyrotropin-releasing hormone and those to vasoactive intestinal peptide and luteinizing hormone-releasing hormone in acromegaly.

There is an almost general agreement on the clinical significance of TRH and bromocriptine (Br) tests in acromegaly. That is that positive GH responses to these tests (with an increase or a decrease, respectively) are known to be very frequently associated with the presence of PRL-containing somatotroph adenomas of the pituitary. In this context, however, very little is known about the clinical significance of paradoxical GH responses to vasoactive intestinal peptide (VIP) and LHRH in acromegaly. We therefore examined, as the principal objective of this study, whether a relationship exists among the GH (in some cases also PRL) responses to TRH, VIP, LHRH and Br in acromegaly. Another aim of this study was to examine whether a sexual difference exists in GH and PRL secretion in acromegaly. We examined a total of 24 patients comprising 8 men and 16 women. In agreement with previous reports, TRH-responders tended to have a higher level of basal PRL than TRH-nonresponders. In contrast, VIP-responders and LHRH-responders tended to have a lower PRL level than their respective counterparts. Although Br responsiveness was unexpectedly similar between TRH-responders and nonresponders, it was revealed that pure TRH-responders who were not responsive to VIP or LHRH were more sensitive to Br and more hyperprolactinemic than the remaining TRH-responders. This suggests that the simultaneous GH responsivity to VIP and/or LHRH in TRH-responders may be a factor which lowers their Br responsiveness and basal PRL levels. With respect to a sexual difference in GH and PRL secretion, it was revealed that female acromegalics had higher levels of basal GH and PRL than male patients. In addition, it was found that female acromegalics had supernormal levels of basal PRL, but a subnormal PRL responsiveness to TRH. As the major implication of this study, we hypothesize that the positive GH response to TRH associated with a high sensitivity to Br may, as already suggested, be characteristic of PRL-containing somatotroph adenomas, whereas the GH responsivity to VIP, and possibly also to LHRH, co-existing with no or low sensitivity to Br may be a feature of pure somatotroph adenomas. Although this study is devoid of immunohistochemical evidence to support this hypothesis, we suggest that the present in vivo data may be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testings in acromegaly.

Acromegaly↗
PubMed1993

Intrahypothalamic perfusion with interleukin-1-beta stimulates the local release of corticotropin-releasing hormone and arginine vasopressin and the plasma adrenocorticotropin in freely moving rats: a comparative perfusion of the paraventricular nucleus and the median eminence.

It is almost generally accepted that an acute-phase ACTH response induced by interleukin (IL)-1 is mediated principally by CRH release from the hypothalamus. However, the precise cellular site of action of IL-1 in activating the CRH neuronal system remains to be determined. Two likely candidates comprise the paraventricular nucleus (PVN) where CRH neuronal cell bodies are located, and the median eminence (ME) where their nerve endings are terminated. Therefore, in this study we performed a comparative perfusion of the ME and the PVN with increasing concentrations of recombinant human IL-1 beta utilizing the push-pull perfusion technique in freely moving rats. We measured the plasma ACTH and ME and PVN levels of CRH, and also of AVP, because AVP, another secretagogue of ACTH, has its cell body in the PVN and axon terminals partly in the ME. In control groups, the ME or the PVN was perfused with artificial cerebrospinal fluid between 12:00 and 15:00 h, and perfusates and blood samples were collected every 20 min. In the other groups, either the ME or the PVN was perfused with three increasing concentrations (0.1, 1.0, and 10 nM) of recombinant human IL-1 beta dissolved in artificial cerebrospinal fluid only between 13:00 and 14:00 h with all the other procedures run in the same way as in the controls. In the control perfusions, the hypothalamic release of CRH and AVP and the plasma ACTH did not change significantly during the entire period of observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗