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It is almost generally agreed that prostaglandins (PGs), especially PGE2, may play a significant role in mediating corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) secre

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.

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-1β 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-1β 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. In the ME perfusion with IL-1β, 1.0 and 10 nM, but not 0.1 nM, of the cytokine significantly and dose-dependently stimulated CRH and AVP secretions in the ME and the plasma ACTH. ACTH responses during the PVN perfusion with IL-1β were similar to those during the ME perfusion, except that at the PVN the lowest concentration (0.1 nM) of the cytokine was already effective in stimulating ACTH secretion. These in vivo data suggest that IL-1β may act on both the ME and the PVN to stimulate CRH and,’ thereby, ACTH secretions. The secretory response of hypothalamic AVP to IL-1β, which was similar to that of CRH, suggests that not only CRH but also AVP may mediate the IL-1β stimulation of ACTH secretion.

We compared the effects of neonatal androgenization (NA) and estrogenization (NE) on vasoactive intestinal peptide (VIP) levels in the anterior pituitary (AP) and the hypothalamus and on prolactin (PRL) secretion in adult female rats. Twenty-four hours after birth, a total of seven groups were treated as follows. Three NA groups received a single subcutaneous injection of 10, 100, or 1,000 micrograms of testosterone, respectively. Similarly, three NE groups received 1, 10, or 100 micrograms of 17 beta-estradiol, respectively. The remaining one group was injected with oil vehicle only, and served as controls. At 8 weeks of age, animals were sacrificed by rapid decapitation. NA (1,000 micrograms) and NE (100 micrograms) resulted in a similar degree of hyperprolactinemia and hyperestrogenemia, but this effect ratio between NA and NE (about 1:10) was not true with the lower doses, indicating a qualitative difference in the effects of the two treatments. This is in agreement with our previous study. VIP content determined in the suprachiasmatic nucleus, the paraventricular nucleus and the median eminence did not significantly correlate with plasma PRL. In contrast, there were significant correlations among AP VIP, plasma PRL and estradiol. These results suggest the possibility that the NA- and NE-induced hyperprolactinemia may be mediated, at least in part, by a paracrine and/or autocrine effect of the increased AP VIP on the lactotroph which may probably be mediated by hyperestrogenemia. However, the possibility was also suggested that the observed changes in AP VIP were related more to NA and NE's imprinting effects on the developing brain than to the PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to assess the physiological role of neurotensin (NT) in regulating the secretions of luteinizing hormone (LH) and prolactin (PRL), we examined whether the in vivo release of NT from the push-pull cannulated median eminence (ME) was altered in association with the LH and PRL surges in free-moving ovariectomized rats primed with estradiol. For comparison, LH-releasing hormone (LHRH) was also measured in the same perfusates from the ME in which NT was determined. NT and LHRH in the ME started to significantly increase roughly concurrently with the initial significant rises in LH and PRL in the plasma, and the highest levels of the neuropeptides clearly preceded the peak levels of LH and PRL. These in vivo data strongly suggest that NT, independently of or in concert with LHRH, may have a facilitatory role in the generation of estradiol-induced LH surge. In addition, these data may not disagree with a similar facilitatory role of NT in the PRL surge. This is the first characterization of the temporal profile of NT secretion in rat ME in terms of its relationship to the estradiol-induced surges of LH and PRL.

The inhibitory effects of corticosterone, dexamethasone and prednisolone on activity of the hypothalamus-pituitary-adrenal axis were investigated in adrenalectomized rats infused with glucocorticoids for 6 h. Infusion of 202 micrograms corticosterone did not inhibit the plasma ACTH concentration, but 504 micrograms corticosterone significantly suppressed plasma ACTH levels. Infusion of 20 micrograms dexamethasone suppressed markedly the plasma ACTH concentration. These data suggest that the degree of inhibition of dexamethasone on ACTH release is about 25 times greater than that of corticosterone. The CRF content of the hypothalamus was not decreased by the administration of 202 micrograms corticosterone over a 6-hour period, but it was significantly diminished by 504 micrograms corticosterone. Infusion of 504 micrograms dexamethasone did not decrease the hypothalamic CRF content; however, infusion of 5 mg dexamethasone effectively suppressed the hypothalamic CRF content. Infusion of 2.5 mg prednisolone did not either decrease the CRF content. These data suggest that the degree of inhibition of natural steroid at the hypothalamus level is stronger than that of synthetic steroids. In rats pretreated with a single injection of dexamethasone (25 micrograms/200 g body weight) 22 h prior to the experiments, continuous infusion of 318 micrograms of dexamethasone significantly suppressed the hypothalamic CRF content, whereas infusion of 504 micrograms of dexamethasone failed to decrease the hypothalamic CRF content in the rats not pretreated with dexamethasone. This finding suggests that a latent period after the injection of dexamethasone is needed for the appearance of the inhibitory action of synthetic steroids at the level of hypothalamus.

Plasma ACTH and corticosterone were measured under basal conditions and after ether or tourniquet stress during the nadir (a.m.) and zenith (p.m.) of the nycterohemeral pituitary-adrenal cycle. Exogenous ACTH was also given at these 2 times to assess adrenal sensitivity to ACTH and the maximal adrenal capacity for corticosterone secretion. Ether stress caused a greater rise in plasma ACTH in the a.m. than in the p.m., even though basal plasma ACTH and corticosterone concentrations were lower in the a.m. than in the p.m. When given in the p.m., pentobarbital anesthesia depressed plasma corticosterone and ACTH to the a.m. level; under these conditions the rise in plasma ACTH produced by tourniquet stress was the same in the a.m. and p.m. Both tourniquet and ether stresses caused maximal activation of adrenal corticosterone secretion, but ether produced a much greater rise in plasma ACTH. It is concluded that: (1) the greater ether-induced rise in plasma ACTH in the a.m. than in the p.m. is probably due to the lower plasma (and probably tissue) corticosterone concentration at that time; (2) the plasma ACTH concentration for inducing maximal adrenal activation is relatively low; and (3) the higher basal levels of plasma corticosterone in the p.m. than in the a.m. are due to a slight increase in basal ACTH secretion in the p.m.

Only a few reports have appeared which have attempted to determine whether the naturally occurring steroid corticosterone, has the same site of action in the hypothalamus-pituitary-adrenal axis as the synthetic steroid, dexamethasone. The present studies help to define the site of inhibition of both corticosterone and dexamethasone on the hypothalamus-pituitary-adrenal axis. Infusion of 20 or 202 microgram corticosterone over 6 h significantly reduced hypothalamic CRF (corticotropin-releasing factor) content, whereas it did not reduce plasma ACTH levels in normal rats. The finding indicates the possibility that the infusion of corticosterone may decrease the hypothalamic CRF content by reducing CRF production or enhancing intracellular and/or extracellular CRF degradation. On the other hand, infusion of 20 microgram dexamethasone for 6 h to normal rats significantly decreased plasma ACTH levels, but did not alter the hypothalamic CRF content. This finding indicates that dexamethasone may inhibit the release and/or production of ACTH in the anterior pituitary. In addition, relatively large doses of corticosterone (504 microgram/rat) and dexamethasone (202 microgram/rat) may suppress CRF content and ACTH release at the level of both the hypothalamus and anterior pituitary.