Decreased prostaglandin E2 synthesis by lens epithelial cells cultured on heparin-surface-modified poly(methyl methacrylate).

PURPOSE: To evaluate whether heparin surface modification reduces prostaglandin E2 (PGE2) synthesis by lens epithelial cells (LECs) after intraocular lens (IOL) implantation. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: The prostaglandin E2 (PGE2) concentration was determined in an incubation medium of human cataract LECs cultured on heparin-surface-modified (HSM) poly(methyl methacrylate) (PMMA) plates at 1, 2, 3, and 4 weeks of culture. A medium without heparin served as a control. RESULTS: The PGE2 concentration was significantly lower in the HSM than in the control medium at 3 and 4 weeks of culture. CONCLUSION: The results are consistent with the clinical observation of significantly decreased inflammation in eyes with HSM IOLs, indicating that such modification increases PMMA's biocompatibility with LECs.

Evidence for a regional distribution of hyaluronic acid in the rat brain using a highly specific hyaluronic acid recognizing protein.

By means of a highly specific hyaluronic acid-recognizing protein the localization and regional distribution of hyaluronic acid was demonstrated in the tel- and diencephalon and in the midbrain of the adult rat nervous system. Histochemistry revealed labeling associated with the plasma membrane in highly discrete nerve cell bodies of the frontoparietal cortex, the red nucleus, the zona reticulata of the substantia nigra, the oculomotor nucleus and the reticular thalamic nucleus. A strong labeling without association with perikarya was demonstrated in the subgranular zone of the dentate gyrus of the hippocampal formation. The present results open up the possibility that the hyaluronic acid found in high concentrations associated with some perikarya may have a special role in plasticity responses in these discrete nerve cell populations.

Immobilization stress induces vasodepressor and altered neuroendocrine responses in the adult stroke-prone spontaneously hypertensive male rat.

The effects of acute (1 h) and daily repeated immobilization stress (14 days, twice-daily, 1 h) were studied on arterial blood pressure and heart rate and on the blood levels of several hormones in the adult (5 months old) stroke-prone spontaneously hypertensive rat (SHRSP) and in the age-matched normotensive Wistar-Kyoto (WKY) rat. The major result was the development of a long-lasting vasodepressor response in the SHRSP, while the same acute or repeated immobilization stress in the WKY rat led to the development of a prolonged vasopressor response. Differential changes to stress were also observed in practically all neuroendocrine axes with the exception of the pituitary-adrenal axis. The vasodepressor response to immobilization stress in SHRSP may be related to an exaggerated defence-like reaction causing an enhanced vasodilation in the skeletal muscle beds associated with a tachycardia similar to that in the normotensive control rats.

Histochemical identification of hyaluronan in the rabbit anterior segment during the healing period after extracapsular lens extraction.

Extracapsular lens extractions were performed in rabbits. The eyes were examined at different time intervals after surgery with a histochemical method visualizing hyaluronan. There was positive staining for hyaluronan in the wound region from 2 to 90 days postoperatively. The staining was most intense and widespread between 7 and 14 days after surgery. A hyaluronan staining in the corneal stroma extended from the wound towards the central cornea 4 to 14 days postoperatively. The iris showed increased staining on the second postoperative day, but much less so at the other times studied. Cells on the posterior lens capsule were surrounded by hyaluronan from the seventh postoperative day throughout the observation time up to 90 days postoperatively. It is concluded that hyaluronan reacts during corneal wound healing.

Hyaluronic acid in the rabbit cornea after excimer laser superficial keratectomy.

Hyaluronic acid (HA) is not normally found in the corneal stroma. Rabbit corneas were examined for the presence of stromal HA after excimer laser treatment. One eye in each of 28 rabbits received a 60 microns deep superficial keratectomy with the excimer laser. After 1, 8, 21, and 60 days, the corneas were analyzed by quantitative and histochemical methods specific for HA. A statistically significant increase in the HA concentration compared to the baseline amount in the untreated fellow eye was seen at 8, 21, and 60 days. HA was visualized histochemically in the anterior stroma of the excimer-treated eyes at all times tested. The presence of HA after excimer surgery may influence the hydration, thickness, and transparency of the cornea. The reactive production of HA in the stroma may represent a nonspecific corneal tissue response to injury.

Evidence of hyaluronic acid and hyaluronic acid binding sites on human corneal endothelium.

A highly specific hyaluronic acid (HA) recognizing protein (HABR) was used to study whether the human corneal endothelium is covered by HA and to quantify the amount. Tritiated high molecular weight HA was used to determine the capacity of the human endothelium to bind exogenous HA. Human corneas were obtained from keratoconus patients having corneal transplantation and from postmortem eyes. The corneas were immersed in a 4% formaldehyde solution containing 1% cetylpyridine chloride for histochemistry, frozen for biochemistry, or used for 3H-HA (Mr 3 x 10(6) binding. For the biochemical determinations, 125I-labeled HABR was used. Tritiated HA was used for the binding experiment. A specific layer of HA covering the endothelial cells of the corneal buttons was demonstrated. The biochemical analysis also revealed the presence of HA. Finally, the human endothelial cells had specific hyaluronic acid binding sites.

Fibrinous reaction on implanted intraocular lenses. A comparison of conventional PMMA and heparin surface modified lenses.

We studied the fibrinous reaction after intraocular lens (IOL) implantation in the posterior chamber of cynomolgus monkeys. In 50% of the eyes, we implanted an IOL made of conventional poly-(methyl methacrylate) (PMMA); in the remaining eyes we implanted a PMMA IOL with a heparin modified surface. Two, 4, 8, and 18 weeks after surgery the eyes were examined by slitlamp for fibrinous reactions on and around the IOL surface. At weeks 4, 8, and 18 there was a marked decrease in fibrinous reaction in the eyes with a heparin surface modified IOL. The results of this study accord with earlier findings that heparin surface modification improves the biocompatibility of the IOL.

Reactive formation of hyaluronic acid after small and large lens injury.

The reactive production of hyaluronic acid was studied in the rabbit lens following a 4 mm in diameter anterior lens wound, and following a large lens wound (extracapsular cataract extraction). Furthermore, human post-mortem after-cataract specimen were also studied. The hyaluronic acid was localized histochemically using a new specific technique. Hyaluronic acid in the small wound was localized in the primary sealing plug that precedes the reepithelialization and new capsule formation. In the large wound hyaluronic acid was found around the cells proliferating on the posterior capsule. The same was true in the human after-cataract specimen. It was concluded that the primary wound sealing and the posterior capsule cellular outgrowth constitute similar cellular responses.

Reactive formation of hyaluronic acid in the rabbit corneal alkali burn.

The presence and distribution of reactively formed hyaluronic acid (HA) was assessed in the rabbit cornea following a penetrating alkali burn. The injury was inflicted by applying a round, 5.5 mm, filter paper soaked in 1 N NaOH centrally on the cornea for 60 seconds. Biochemical analysis revealed a significant increase of HA two weeks after injury, a peak concentration after 1 month, and a decrease again at three months. Histochemical analysis revealed the presence of hyaluronic acid in the healing epithelium, in the repopulating keratocytes/fibroblasts, and in the cells forming the retrocorneal membrane. Extensive amounts filled lacunae in the stroma as well as the spaces between collagen lamellae. A slow restoration of normal appearing corneal stroma took place at the periphery. Significant staining for HA in lacunae was present centrally in the wound after three months.

Inflammatory response in the rabbit eye after intraocular implantation with poly(methyl methacrylate) and heparin surface modified intraocular lenses.

Early inflammatory responses in rabbit eyes after anterior chamber implantation with poly(methyl methacrylate) (PMMA) and heparin surface modified intraocular lenses (IOLs) and after cataract extraction and implantation with PMMA and heparin surface modified intraocular lenses (IOLs) were investigated between 1 and 30 days postoperatively. The number of white blood cells in the aqueous humor, the distribution of white blood cell subsets, and the interleukin-1 (IL-1b) levels were studied. At one day postoperatively, there was a significantly smaller number of white blood cells in eyes with heparin surface modified IOLs than in eyes with PMMA IOLs after both anterior chamber implantation and cataract surgery and capsular bag implantation. At one day postoperatively, 87% of the cell population in eyes with PMMA IOLs were neutrophilic granulocytes. Two days later the neutrophilic granulocytes had decreased to 13% and at seven days they were gone. At 14 days the frequency was 7% and at 30 days it was 27%. The fraction of monocytes/macrophages in the cell population was 9% (day 1), 79% (day 3), 94% (day 7), 81% (day 14), and 72% (day 30). The fraction of lymphocytes was low throughout the test period (1% to 10%). The percentages were almost the same in eyes with heparin surface modified IOLs and there was no significant difference in the distribution of white blood cell subsets between the two lens materials. The IL-1 was not detected in any of the samples (day 3, day 7, and day 30). Inactivated macrophages and/or levels under detection limits could be the reason.(ABSTRACT TRUNCATED AT 250 WORDS)

On the role of neuropeptide Y in information handling in the central nervous system in normal and physiopathological states. Focus on volume transmission and neuropeptide Y/alpha 2 receptor interactions.

The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.

Effects of withdrawal from chronic exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat.

A 48 h but not a 72 h or 7 day withdrawal from chronic exposure to cigarette smoke was associated with increased noradrenaline levels (quantitative histofluorimetry) in the subependymal layer (SEL) of the median eminence, the anterior periventricular hypothalamic region (PV I) and the parvocellular part of the hypothalamic nucleus (PA FP) and an increased noradrenaline utilization (tyrosine hydroxylase inhibition by alpha MT) in the SEL and the PV I. Following a 48 h or 72 h but not a 7 day withdrawal from chronic exposure to cigarette smoke an increased catecholamine utilization was found in the medial palisade zone (MPZ) of the median eminence. Reduced serum prolactin, FSH and corticosterone levels were found following a 48 h withdrawal from chronic exposure to cigarette smoke. Following a 72 h withdrawal from chronic exposure to cigarette smoke a reduced concentration of serum prolactin was noted. Chronic exposure to cigarette smoke reduced serum TSH levels and lead to a tolerance development with regard to noradrenaline levels and utilization within the preoptic region with the exception of the periventricular preoptic region. The finding of special interest in the present study is the demonstration of a highly significant lowering of corticosterone serum levels despite maintained blood levels of ACTH as seen 48 h following withdrawal. It is suggested that this type of endocrine change may lead to changes in fear-motivated behaviour and contribute to behavioural withdrawal reactions. The maintained reductions of serum prolactin levels found after 48 h and 72 h of withdrawal from cigarette smoke exposure (cf. Andersson et al. 1985a) is discussed in terms of an increased catecholamine utilization in the medial palisade zone of the median eminance. This activation is suggested to be caused by the development of a prolactin receptor supersensitivity within the medium eminence. The present evidence indicates withdrawal effects mainly in the noradrenaline nerve terminals of the subependymal layer of the median eminence, the anterior periventricular hypothalamic region and the parvocellular part of the paraventricular hypothalamic nucleus which inter alia are involved in regulation of ACTH secretion (cf. Andersson et al. 1985a).

Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat.

The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease.

Reciprocal interactions between alpha 2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat. A biochemic and autoradiographic analysis.

Interactions between a alpha 2-adrenoceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (3H-PAC; alpha 2-adrenoceptor agonist), idazoxan (3H-IDA; alpha 2-adrenoceptor antagonist) and iodinated neuropeptide Y (125I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10(-8) M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10 nM) increased the KD value of 3H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25 nmol) did not change the 3H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10(-4) lowered the affinity of 3H-PAC binding. NPY (10 nM) had no additional effect, nor did NPY influence the GTP induced shift in potency of clonidine to displace 3H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10 nM) significantly reduced 3H-PAC binding (2 nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75 nmol) or in vitro (10 nM) the binding of 125I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 micrograms i.c. 24 h) 125I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. These results provide support for a direct intramembrane interaction between the alpha 2-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation.

Regional differences in glucocorticoid receptor immunoreactivity among neuropeptide Y immunoreactive neurons of the rat brain.

By means of two-colour immunocytochemistry using a mouse monoclonal antibody directed against the rat liver glucocorticoid receptor (GR) and a rabbit polyclonal neuropeptide Y (NPY) antiserum combined with the biotin-avidin immunoperoxidase and a double immunofluorescence procedure, it has been possible to demonstrate nuclear GR immunoreactivity (IR) in neurons showing cytoplasmatic NPY IR in rat brain. The majority of NPY immunoreactive perikarya of the medial parvocellular part of the arcuate nucleus, locus coeruleus and the rostral and caudal part of the ventrolateral medulla oblongata contained strong nuclear GR IR. Many of the NPY immunoreactive neurons present in the subnuclei of the nucleus tractus solitarius also contained nuclear GR IR, while most of the NPY immunoreactive perikarya of the cerebral cortex and all of the neostriatum appeared to lack GR IR. These results indicate that NPY immunoreactive neurons in the upper and lower brain stem, but not in the cerebral cortex and in the neostriatum may be directly involved in mediating central effects of glucocorticoids.

Neuroendocrine actions of nicotine and of exposure to cigarette smoke: medical implications.

Over many years a large number of studies have demonstrated that nicotine and exposure to cigarette smoke produce marked neuroendocrine changes in animals and in man. The initial effects of nicotine are characterized by a marked hypersecretion of ACTH, vasopressin, beta-endorphin, prolactin and LH. Many of these very acute stimulatory effects of nicotine rapidly disappear, probably due to a desensitization of the central nicotinic cholinergic receptors involved. Instead, upon acute intermittent treatment with nicotine or exposure to cigarette smoke, an inhibition of prolactin, LH and TSH secretion occurs, which is associated with maintained hypersecretion of corticosterone. These effects are probably mediated via activation of central cholinergic receptors of the ganglionic type. Evidence indicates that the inhibitory effects of nicotine on LH and prolactin secretion are produced via an activation by these nicotinic receptors of the tubero-infundibular dopamine neurons, releasing dopamine as a prolactin inhibitory factor. Dopamine inhibits LHRH release via an axonic interaction involving D1-like dopamine receptors in the median eminence. It therefore seems possible that the reduced fertility found in heavy smokers may be counteracted by D1 receptor antagonists. The symptoms associated with glucocorticoid hypersecretion induced by nicotine is discussed considering not only the peripheral side effects but also permanent deficits in hippocampal glucocorticoid receptors and loss of hippocampal neurons. In view of the important influence of hormones on immune functions, it seems likely that smoking will cause disturbances in immune responsiveness. Finally, the nicotine-induced alterations of neuroendocrine function, especially in the pituitary-adrenal axis and in vasopressin release, may also lead to behavioural consequences in smokers, especially in the withdrawal phase.

Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat.

Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of chronic toluene exposure on central monoamine and peptide receptors and their interactions in the adult male rat.

The effects of chronic toluene exposure (CTE) (80 ppm, 6 h/day, 5 days/week, 3 months) were studied on neuropeptide and 5-hydroxytryptamine receptors, on protein phosphorylation levels and on catecholamine levels in various brain regions in the 15-month-old male rat. Behavioral parameters and serum levels of hypophyseal hormones and corticosterone were also analyzed. CTE selectively reduced [3H]neurotensin [( 3H]NT) binding in the basal layers of the orbital cortex. Instead, CTE increased the binding of [3H]etorphine in the nucleus accumbens and of [125I]vasoactive intestinal polypeptide [( 125I]VIP) in the area postrema and hypoglossal nucleus. Acute treatment with the irreversible monoamine receptor antagonist N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) increased the binding of [3H]NT in the orbital cortex in toluene exposed rats as compared with the reduced [3H]NT binding obtained in air exposed rats treated with EEDQ. Furthermore, the EEDQ induced increase in [125I]VIP binding in the area postrema and the hypoglossal nucleus was replaced by a reduced binding of [125I]VIP in EEDQ-treated CTE rats. CTE produced an overall increase in calcium-induced back phosphorylation and an overall decrease in cyclic adenosine monophosphate-induced back phosphorylation in the frontoparietal cortex. Noradrenaline stores tended to be reduced within various hypothalamic subnuclei and the serum prolactin levels were increased following CTE. However, no marked effects of CTE were seen on the behavioral parameters. In conclusion, the regional selectivity of CTE in disturbing [3H]NT and [125I]VIP binding may be due to the demonstrated vulnerability of monoamine-neuropeptide interactions to toluene.

Receptor autoradiographical evidence of a preferential reduction of binding sites for atrial natriuretic factor in renal papilla of the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) as well as in the pathophysiological states with volume retention, high levels of atrial natriuretic factor (ANF) do not produce adequate diuresis and natriuresis. We have investigated the question whether the reduced effectiveness of ANF could be due to a reduction of the ANF binding. Evidence is provided by quantitative autoradiography with [125I]ANF than higher ANF plasma levels in SHRSP compared to normotensive WKY rats are associated with a reduced number of binding sites (25%) in the renal papilla as well as in the subfornical organ (69%). This could contribute to the reduced response of ANF in SHRSP.

Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male rat.

Male rats were treated acutely with nicotine (4 x 2 mg/kg, 30-min time intervals, total treatment time 2 h) or exposed to cigarette smoke from 4 x 1 cigarette (30-min time intervals, total treatment time 2 h). Some rats were pretreated with the D1 dopamine (DA) receptor antagonist SCH 23390 (0.1-3.0 mg/kg, i.p.), or with the D2 DA receptor antagonists remoxipride and raclopride (1 mg/kg, i.p.), or with the 5-hydroxytryptamine 2 (5-HT2) receptor antagonist ketanserin (0.3 mg/kg, i.p.) 5 min before nicotine treatment or the acute intermittent exposure to cigarette smoke. Some rats were treated with the D1 DA receptor agonist SK&F 38393 (1-10 mg/kg, i.p.) 15 min, 30 min or 2 h before decapitation. Hypothalamic and pre-optic catecholamine (CA) levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline (NA) nerve terminal systems. Serum thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), vasopressin, corticosterone and testosterone levels were determined by radioimmunoassay procedures. Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels. Nicotine treatment also increased serum corticosterone levels. Pretreatment with the D1 DA receptor antagonist SCH 23390 (1-3 mg/kg) counteracted the lowering of serum LH, but not of prolactin and TSH levels induced by nicotine or exposure to cigarette smoke. SCH 23390 alone (1-3 mg/kg) increased serum TSH levels. Remoxipride, raclopride or ketanserin did not counteract any of the neuro-endocrine actions induced by nicotine treatment. However, ketanserin alone lowered serum prolactin levels. SK&F 38393 increased serum TSH, prolactin and LH levels. It was found that nicotine treatment and exposure to cigarette smoke with few exceptions produced a depletion of CA stores in NA and DA nerve terminals of the hypothalamus, pre-optic area and median eminence which was counteracted by SCH 23390 (1 mg/kg) but not by remoxipride, raclopride (1 mg/kg) or ketanserin (0.3 mg/kg). The results indicate that D1 but not D2 DA or 5-HT2 receptors may modulate the NA and DA release in the median eminence, the hypothalamus and the pre-optic area induced by nicotinic cholinoceptor activation. Furthermore, D1 DA receptors in the median eminence may at least in part mediate the inhibitory effects of nicotine on LH but not on TSH and prolactin secretion, although there appears to exist a D1 DA receptor in the median eminence which inhibits TSH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)