Median Eminence Of Hypothalamus Research Articles

Hypo - and hyperinsulinemia as regulatory factors of somatostatin secretion in the hypothalamus median eminence

Hypo - and hyperinsulinemia as regulatory factors of somatostatin secretion in the hypothalamus median eminence

Immunohistochemical investigations of the IGF-I receptors on the surface of ependymal cells of the hypothalamus median eminence

Immunohistochemical investigations of the IGF-I receptors on the surface of ependymal cells of the hypothalamus median eminence

The Nature and Distribution of Gonadotropin-Releasing Hormones in Brains and Plasma of Ranid Frogs

Highly specific antisera and reversed-phase HPLC were used to examine the nature and distribution of gonadotropin-releasing hormone (GnRH) in the brains and plasma of three species of Rana frog previously reported to vary in the types and brain distributions of GnRH. The three species examined, Rana pipiens, Rana esculenta, and Rana ridibunda, exhibit differences in total concentration and relative concentrations of GnRH in brain areas, but all three contain the mammalian and chicken-II forms of GnRH (mGnRH and cGnRH-II). Both forms were found in the telencephalon and diencephalon, but mGnRH is consistently the most abundant form in the preoptic-hypothalamic area (e.g., ratios of mGnRH:cGnRH-II > 3:1 in hypothalamus-median eminence), whereas, cGnRH-II is the most abundant in the telencephalon and the only form measured in the cerebellum and medulla. The total content of cGnRH-II in the whole brain is about 1.5-2 times higher than that of mGnRH, due to the larger size of the areas outside the preoptic-hypothalamic area. These general patterns were the same for adults and juveniles. We found no evidence of a third form of GnRH corresponding to salmon GnRH in hypothalamus or other brain areas of R. esculenta as previously reported. These analyses also revealed the presence of both forms of GnRH in plasma draining the hypothalamic area, but the concentration of cGnRH-II is relatively higher than that in the corresponding hypothalamic tissue, suggesting differentially greater release or slower degradation of this form. These results do not support the conclusion that the ranid frogs are highly variable in the nature and distribution of GnRH in the brain, although they suggest that both forms of GnRH are potentially involved in the direct regulation of pituitary gonadotropes.

Role of the hypophyseal neurointermediate lobe in the dynamic release of prolactin

The dynamic release of prolactin (PRL) occurs in a region of the anterior pituitary lobe (AP) that receives its blood supply primarily from the hypophyseal neurointermediate lobe (NIL) via the short portal vessels. This relationship, coupled with a growing body of supportive evidence, suggests that the hypophysiotropic signal mediating the massive discharge o f AP PRL derives from the NIL rather than the hypothalamic median eminence, as previously believed. Moreover, a major component of this signal appears to be a-MSH.

Prostaglandins mediate the ACTH response to interleukin-1-beta instilled into the hypothalamic median eminence.

Interleukin-1 beta (IL-1 beta) is a potent ACTH secretagogue which activates the release of hypothalamic CRH. Direct injections of IL-1 beta into the hypothalamic median eminence (ME), a site which lacks a blood-brain barrier, has been shown to rapidly induce ACTH secretion. Therefore, the ME is a likely site whereby circulating IL-1 beta can access the brain to stimulate CRH and, consequently, ACTH secretion. To further evaluate this hypothesis, an angular stereotaxic approach was developed to localize the spread of IL-1 beta to the ME and to optimally separate the injectate from the hypothalamic paraventricular nucleus (PVN), another proposed site of IL-1 action. Studies of the diffusion of [125I]-IL beta (100 nl delivered over 60 s) showed that 97% remained within 200 microns of the ventral surface of the hypothalamus and 87% was contained within a radius of 550 microns of the injection site in the sagittal plane. Additional rats received recombinant human IL-1 beta (0.2-25.0 ng in 100 nl) into the ME (intra-ME). Plasma ACTH levels were significantly elevated by a much lower dose (0.5 ng, p < 0.001) of IL-1 beta than that previously reported. Responses appeared to be dose-dependent and ACTH was maximally stimulated by 2.0 ng IL-1 beta. Also, immunocytochemically labelled CRH in the ME was markedly depleted after intra-ME IL-1 beta. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, has been shown to block both the induction of CRH secretion by IL-1 beta from hypothalamic explants, as well as the ACTH response to intravenous IL-1 beta. Thus, indomethacin was used to determine whether PGs are mediators of the ACTH response to IL-1 beta delivered into the ME. The ACTH response was abolished (p < 0.005) when a low dose of indomethacin (1 mg/kg i.v.) was administered 20 min before intra-ME IL-1 beta (25 ng). Finally, plasma ACTH was elevated in a dose-dependent manner by the intra-ME administration of PGs. The hierarchy of ACTH responses to PGE2 were: CSF < 0.5 micrograms (p < 0.001) = 2.0 micrograms < 4.0 micrograms (p < 0.05). Responses to PGF2 alpha were: CSF < 0.5 micrograms (p < 0.001) < 2.0 micrograms (p < 0.05) = 4.0 micrograms. Since these PGs appear to activate different second-messenger systems, a submaximal dose of each was administered alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma CRH response to water immersion-restraint stress in rats bearing a hypothalamic knife cut.

We reported earlier that the plasma level of corticotropin-releasing hormone (CRH) remained high 120 min after the onset of such strong sustained stress as ether-laparotomy or water immersion-restraint, which reflected the persistent secretion of CRH from the hypothalamic median eminence (ME). We investigated the change in plasma CRH during water immersion-restraint stress in rats bearing an anterolateral cut around the medial basal hypothalamus (MBH) which cuts the CRH neurons from the PVN to the ME. Concentrations of CRH in the hypothalamus, extrahypothalamic tissues and peripheral blood were measured by radioimmunoassay. Plasma ACTH was measured with an immunoradiometric assay kit. Plasma baseline ACTH and CRH concentrations did not differ significantly in the sham vs. cut groups. At 120 min after the onset of stress, plasma ACTH concentrations were definitely higher in both groups. In the cut group, plasma CRH at 120 min after stress did not differ significantly from the baseline level, whereas plasma CRH at 120 min was definitely higher in the sham group. Baseline CRH concentrations in the ME did not differ greatly in the two groups. CRH concentrations in the ME of both groups had decreased appreciably 120 min after the onset of stress as compared with baseline CRH, and the CRH decrease was greater in the cut group than in the sham group. CRH in the neurointermediate lobe (NIL) and adrenal gland of both groups showed no significant change at 120 min, compared with the control. These findings confirm that the continuous CRH increase in plasma during sustained stress is derived mainly from the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of systemic administration of 6-hydroxydopamine, 6-hydroxydopa and 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) on tuberoinfundibular dopaminergic neurons in the rat

Using systemic route of administration, the effects of several neurotoxins on hypothalamic tuberoinfundibular dopaminergic neurons were focused in this study. 6-Hydroxydopamine (6-OHDA, 10 or 100 mg/kg b.wt., i.v. or ip) produced a dose (37 vs. 50%)- and time (41 to 29% from day 4 to day 9)-dependent depletion of hypothalamic median eminence concentrations, and increases of serum prolactin levels in ovariectomized rats. Other central dopaminergic neurons, however, were not significantly affected. Similar treatment with 6-hydroxydopa (6-OHDOPA) were less effective. On the other hand, treatments of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP, 10 mg/kg b.wt./day, ip) for 7 or 14 days produced significant decreases of dihydroxyphenylacetic acid (DOPAC) levels in the median eminence and periventricular regions, and increases in serum prolactin levels. Other central dopaminergic neurons were not significantly affected, though. These results suggest that systemic administration of 6-OHDA, 6-OHDOPA, or MPTP, can produce specific destructive effects on the tuberoinfundibular dopaminergic neurons.

Mercury in the Rat Hypothalamic Arcuate Nucleus and Median Eminence after Mercury Vapor Exposure

A histochemical technique has been used to reveal mercury deposits in the hypothalamic arcuate nucleus and median eminence of adult male rats. After exposure to long-term, low-level or short-term, high-level mercury vapor, silver-enhanced mercury grains were found in neurons of the arcuate nucleus. In addition mercury deposits were found in tanycytes, ciliated ependymal cells, and in the walls of capillaries. The mechanisms underlying uptake and possible induction of toxic effects are discussed.

The Median Eminence as a Site for Neuroendocrine Control of Reproduction in Hens

Based on events occurring during the genesis of a preovulatory surge of luteinizing hormone (LH) and an ovulatory failure of central origin, the hypothalamic median eminence (ME) is probably a major neuroendocrine control site for reproductive activity in the hen. The ratio of facilitatory to inhibitory (F:I) inputs on LH-releasing hormone (LHRH) neuronal terminals is an important determinant of the ME control site. The word “facilitatory” is defined as “stimulatory or increasing responsiveness to inputs”. A relative increase in the F:I ratio of inputs on LHRH neuronal terminals at the ME is apparently involved in the genesis of the preovulatory surge of LH. Both an increase in neuropeptide Y (NPY) facilitatory inputs and a decrease in β-endorphin (βEND) inhibitory inputs to ME-LHRH neuronal terminals are involved in the increase in the F:I ratio preceding the preovulatory surge of LH. Although the NPY component of this ratio (F) is apparently driven by the preovulatory surge of progesterone (P4) itself, its βEND component (I) might be related to the preovulatory surge of estradiol accompanying or preceding that of P4. As the egg-producing life of the hen progresses, a relative decrease in the F:I ratio on ME-LHRH neuronal terminals occurs. As a consequence of this decrease, stress-related inputs (e.g., feed restriction) can induce an hypothalamic failure of central origin in laying hens ending their 1st yr of production, but not in birds at the start of their egg-laying life. An increase in ME dopaminergic inhibitory inputs (I) on LHRH neuronal terminals is an apparent cause of the ovulatory failure induced by feed restriction. An additional cause might be the decrease in the ready releasable pool of LHRH at the ME. Thus, the ME is probably a major neuroendocrine control site for reproductive activity in the hen.

Neuropeptide Y Regulation of LHRH Release in the Median Eminence: Immunocytochemical and Physiological Evidence in Hens

It has been suggested that hypothalamic median eminence (ME) might be a control site for luteinizing hormone-releasing hormone (LHRH) release. Thus, stimulatory and/or inhibitory inputs acting at this site might be involved in regulating LHRH release from the ME and, therefore, luteinizing hormone (LH) release from the anterior pituitary. Since a role for neuropeptide Y (NPY) on LH release has been suggested, we have hypothesized that NPY might act in the ME to control preovulatory LHRH release in hens. To examine this possibility we have determined: (a) the immunocytochemical distribution of LHRH and NPY in the ME of the hen, (b) the basal and NPY-stimulated release of LHRH in vitro from the ME of hens undergoing a natural or a premature preovulatory surge of LH, and (c) the tissue content of LHRH and NPY in microdissected MEs, at various times before and during a natural or a premature preovulatory surge of LH. A potential role for NPY on LHRH release in the ME is suggested for the following reasons. (a) There are opportunities for synaptic interactions between NPY and LHRH-containing axons at this site. LHRH-containing cell bodies localized in the anterior hypothalamus/medial preoptic area project to the ME. NPY-containing perikarya, concentrated in the ventromedial aspect of the arcuate nucleus, might contact LHRH processes going to the ME and/or might themselves send axons to the ME, (b) Addition of NPY to the incubation media increases LHRH release from microdissected ME tissue of hens killed at the time of the natural preovulatory surge of LH, but not in hens killed 7 h before the occurrence of this surge. However, the stimulatory effect of NPY on LHRH release can be induced at this latter time when a premature LH surge is elicited. While the natural preovulatory surge of LH occurs 4 h before the second ovulation in a sequence (C2 ovulation), administration of progesterone (P4) 10-14 h before the expected natural C2 ovulation advances the natural LH surge by 7-8 h. Thus, NPY might act as a physiological stimulus of LHRH release at the ME during the preovulatory surge of LH. This is suggested since in vitro basal LHRH release from denervated ME tissue does not change before and during the natural or the premature LH surge. Therefore, preovulatory release of LHRH in vivo might be under a continuous drive from stimulatory inputs to the LHRH neuron and NPY might be one of these stimulating factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of ether-laparotomy and water immersion-restraint stress on CRH concentration in the hypothalamus, extrahypothalamic tissues and peripheral blood.

The effect of sustained stress on the plasma CRH level was studied in rats subjected to the stress of laparotomy conducted under ether anesthesia or water immersion-restraint. The role of AVP in ACTH secretion during such stress was also investigated. Concentrations of CRH and AVP in the hypothalamus, extrahypothalamic tissues and peripheral blood were measured by radioimmunoassays. Persistent secretion of ACTH was observed from 10 or 30 min to 120 min after the onset of each stress. Plasma CRH levels rose significantly 10 min after the onset of ether-laparotomy stress and remained significantly elevated at 120 min compared with controls. In the animals subjected to water immersion-restraint stress, plasma CRH tended to increase during the time course of the stress, reaching levels that were at least two times higher than the control. CRH concentrations in the median eminence (ME) during both types of stress decreased significantly at 120 min. In the ether-laparotomy stressed rats, CRH in the neurointermediate lobe (NIL) decreased significantly at 120 min, similar to the ME. Although a significant change in the adrenal CRH content was observed in the ether-laparotomy stressed rats, the involvement of adrenal CRH in ACTH secretion is unlikely as the absolute change in CRH was very small. These findings suggest that continuous CRH increase reflects a persistent secretion of CRH from the hypothalamic median eminence to the hypophysial portal vessels. It is possible that CRH secretion from the posterior pituitary gland is at least partly responsible for the persistent plasma ACTH increase in ether-laparotomy stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of the hypothalamo-pituitary-adrenocortical axis by the central serotonergic pathway: involvement of endogenous corticotropin-releasing hormone but not vasopressin.

Many reports indicate that serotonin plays a role in the regulation of the hypothalamo-pituitary-adrenocortical axis. The present study was designed to elucidate whether the activation of the central serotonergic pathway enhances adrenocorticotropin and corticosterone secretion, and if so, whether the CRH and vasopressin neuronal systems could be mediating this effect. Intraperitoneal administration of a low dose of L-5-hydroxytryptophan (an aromatic L-amino acid precursor of serotonin synthesis; 20 mg/kg bw, 30 minutes before the sacrifice) in rats pretreated with pargyline (a brain monoamine oxidase inhibitor, which enhances monoamine activity; 75 mg/Kg bw, 16 hours before the sacrifice) and carbidopa (a peripheral active inhibitor of the decarboxylation of aromatic L-amino acids, which would permit more monoamine precursor to be available to the brain; 50 mg/Kg bw, 90 minutes before the sacrifice) increased ACTH and corticosterone secretion in plasma. Such an effect was partially blocked by metergoline (a serotonin type-1 and-2 receptor blocker; 1 mg/Kg bw, 90 minutes before the sacrifice), but not by spiperone (a serotonin type-2 and dopamine receptor antagonist; 0.5 mg/Kg bw. 90 minutes before the sacrifice). The activation of the central serotonergic system enhanced the CRH content in the median eminence, whereas it decreased the content of this neuropeptide in the medial basal hypothalamus. These effects were fully abolished by metergoline, but not by spiperone pretreatment. The activation of the serotonergic pathway did not influence the vasopressinergic neuronal system. In vitro experiments using hypothalamic-median eminence fragments incubated with serotonin solutions indicate that this monoamine possesses a CRH releasing effect at concentrations of 1 microM or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Neuropeptide Y Precursor-Immunoreactivity in the Hypothalamic Dopaminergic Tubero-Infundibular System during Lactation in Rodents*

Evidence from physiological studies in rats shows that neuropeptide Y (NPY) has marked neuroendocrine effects on anterior pituitary function, and especially on LHRH and LH secretions. However, previous immunohistochemical studies in rats have revealed only scarce NPY-axons of medullary origin in the external zone of the hypothalamic median eminence, the common termination site of neuroendocrine adenohypophysiotropic systems. In view of this apparent contradiction, we used light microscopic immunohistochemistry to reassess the distribution of NPY in the hypothalamus of rodents of both sexes under physiological (estrous cycle in rats, pregnancy in rats, and lactation in both rats and mice) and experimental (gonadectomy in rats and adrenalectomy in both rats and mice) conditions with alterations of reproductive functions. We reasoned that such manipulations could induce changes in immunoreactivity in the NPY system involved in neuroendocrine regulation and would thus make it apparent to us. We show here that immunoreactivity for NPY and its carboxyterminal precursor-associated peptide are dramatically increased in the external median eminence of lactating female animals when compared to the other animal groups. This NYP-precursor-immunoreactivity is present, throughout lactation, in the tyrosine hydroxylase-immunoreactive (and therefore possibly dopaminergic) tubero-infundibular system. This immunoreactivity disappears rapidly from the median eminence after pup-removal. These observations suggest a role for NPY-precursor-derived peptides in the control of the suckling-induced PRL secretion and also demonstrate the chemical plasticity of the median eminence during a normal physiological event. Since in nonlactating animals and especially in normal cycling females NPY-precursor-immunoreactivity was detected in the system of medullary origin only, we conclude that, by exclusion, this system might be the one responsible for modulating gonadotropic secretion at the median eminence and/or pituitary levels.

Hypothalamic Endothelin

Endothelin-3-like immunoreactivity (ET-3-ir) was detected in extracts of rat hypothalamic median eminence, and in the anterior and neurointermediate lobes of the pituitary at levels (ng ET-3/mg protein) exceeding those present in extracts of abdominal aorta. This ET-3-ir appeared authentic because radioimmunoassay (RIA) dose-response curves parallel to those of synthetic ET-3 could be constructed and this ET-3-ir comigrated on C-8 high-pressure liquid chromatography (HPLC) with synthetic ET-3. Endothelin-1-like immunoreactivity, on the other hand, was abundant in extracts of abdominal aorta and cerebral cortex and only minimally present in hypothalamus and anterior pituitary gland. Central administration of 11 and 23 pmol ET-3 resulted in significant (4.2- and 5.7-fold, respectively) elevations of plasma levels of vasopressin. Oxytocin levels were transiently, yet significantly, elevated (1.8-fold) by the higher dose of ET-3. These results, and our findings that central administration of ET-3 inhibits stimulated water drinking, suggest a physiologically important role for endogenously produced endothelin in the central mechanisms regulating fluid and electrolyte homeostasis.

The Androgen-Binding Protein Gene Is Expressed in Male and Female Rat Brain*

Extracellular androgen-binding proteins (ABP) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in liver, are encoded by the same gene. We have now found that the ABP-SHBG gene is also expressed in male and female rat brain. Immunoreactive ABP was found to be present in neuronal cell bodies throughout the brain as well as in fibers of the hypothalamic median eminence. The highest concentrations of immunoreactive cell bodies were located in the supraoptic and paraventricular nuclei. Likewise, ABP mRNA was present in all brain regions examined. Analysis of cDNA clones representing brain ABP mRNAs revealed amino acid sequence differences in brain and testicular ABPs. The protein encoded by an alternatively processed RNA has sequence characteristics suggesting that the protein could act as a competitior of ABP binding to cell surface receptors. These data and gene-sequencing experiments indicate that a specific ABP gene promoter is used for transcription initiation in brain. ABP may function in brain as an androgen carrier protein; however, in view of the widespread presence of ABP and ABP mRNA in brain, the protein may have a much broader, yet unknown, function.

The Adrenocorticotropin Response to Interleukin-1β Instilled into the Rat Median Eminence Depends on the Local Release of Catecholamines*

Interleukin-1 beta (IL-1 beta) is a potent ACTH secretagogue which activates the release of hypothalamic CRF but is unable to cross the blood brain barrier. Recently, it was reported that IL-1 beta, instilled directly into the hypothalamic median eminence (ME), rapidly induced ACTH secretion. Thus, due to the lack of a blood brain barrier the ME appears to be a site whereby iv IL-1 beta can access the brain to stimulate CRF and, consequently, ACTH secretion. To evaluate the role of central catecholamines in this process, 250 g male rats were lesioned with 6-hydroxy-dopamine instilled into the lateral ventricle. Ten days later, rats received recombinant h-IL-1 beta (10 or 30 ng) into the ME and blood was sampled via indwelling jugular cannulae. The ACTH response to IL-1 beta, 30 ng, was reduced by approximately 50% in the lesioned rats (P = 0.05), and it was abolished in those receiving IL-1 beta, 10 ng (P less than 0.05). Moreover, in rats given iv IL-1 beta (1 microgram), 6-hydroxy-dopamine significantly reduced the ACTH response by more than 50% (P less than 0.001). To determine the effect of acute epinephrine depletion, 2,3 dichloro-alpha-methylbenzylamine (DCMB, 60 mg/kg BW) and SKF64139 (SKF) (100 mg/kg BW), inhibitors of the enzyme which converts norepinephrine to epinephrine, were administered ip 4 h before intra-ME IL-1 beta (30 ng). DCMB reduced the ACTH response by 80% and SKF reduced it to its own baseline. LY 10853, which acutely depletes both norepinephrine and epinephrine, also reduced the ACTH response by 80%. Because of the reported capacities of DCMB and SKF to block alpha 2 adrenoreceptors in vitro, yohimbine, an alpha 2 receptor antagonist, was studied. Intra-ME yohimbine failed to inhibit the ACTH response to intra-ME IL-1 beta. In contrast, a significant (P less than 0.01) dose-dependent reduction in the ACTH response to intra-ME IL-1 beta (30 ng) was observed in rats pretreated with either a nonselective alpha or beta adrenoreceptor antagonist (phentolamine, 2-40 micrograms or propranolol, 2-20 micrograms, respectively, into the ME). In contrast, intra-ME phentolamine, 20 micrograms, failed to reduce the ACTH response to iv CRF, 1 microgram/kg BW. Thus, the secretion of ACTH stimulated by the action of IL-1 beta at the ME depends, in part, on the local secretion of norepinephrine and epinephrine interacting with both alpha and beta adrenergic receptors.

Fine Structure of Tyrosine Hydroxylase-like Immunoreactive Neurons and Terminals of the Hypothalamic Arcuate Nucleus and Median Eminence in Young and Aged Rats

Tyrosine hydroxylase (TH)-like immunoreactive neurons, fibers, and terminals in the hypothalamic arcuate nucleus and median eminence of young (8 weeks old) and aged (24 months old) rats were investigated at light and electron microscopic levels by means of the peroxidase anti-peroxidase (PAP) method. In the arcuate nucleus, TH-like immunoreactive neuronal perikarya of young animals contained well-developed cell organelles such as rough-surfaced endoplasmic reticulum (rER), mitochondria, Golgi apparatus, polysomes, as well as dense granules. Immunoreactive neuronal elements appeared as both presynaptic and postsynaptic elements. In aged rats, TH-like immunoreactive neuronal perikarya as well as non-immunoreactive ones were found to include many lysosomes or inclusions, and many neuronal elements with degradative changes were observed. In the external layer of the median eminence of young animals, many immunoreactive nerve endings were found around the pericapillary spaces of portal vessels and often terminated adjacent to the basement membranes of the pericapillary spaces. Immunoreactive fibers having close contact with non-immunoreactive fibers were also observed. In aged animals, degradative changes such as axons with swollen and watery appearance and myelin figures were observed in the neuronal elements, although many immunoreactive nerve endings were seen around the pericapillary spaces.

Reduced aminergic synthesis in the hypothalamus of the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse

Diabetes mellitus is commonly associated with reproductive neuroendocrinopathy in both humans and animal models for the disease. Diabetes-associated reproductive failure in the male is a result of multilevel dysfunction within the hypothalamo-pituitary-testicular axis. In view of the known effects of diabetes on hypothalamic gonadotropin-releasing hormone (GnRH) and gonadotropins in chemically-induced animal models for diabetes, we examined hypothalamic aminergic activities (important to the regulation of GnRH release), circulating gonadotropin levels and testicular morphology in the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse. Groups of 2-5 month old (average age: 3.4 months) and 6-11 month old (average age: 8.8 months) diabetic mice were compared with age-matched non-diabetic (C57BL/KsL(-)+/?) male mice. Diabetic mice in both age groups were markedly obese and hyperglycemic. Hypothalamic serotonin synthesis was inhibited in the preoptic area-anterior hypothalamus (POA-AH) in both 2-5 month old and 6-11 month old diabetic mice as well as in the mediobasal hypothalamus-median eminence (MBH-ME) of 6-11 month old diabetic mice. Catecholamine synthesis (norepinephrine and dopamine) was reduced in the POA-AH of 2-5 month old diabetic mice and in the MBH-ME of 6-11 month old mice. These aminergic changes were associated in 2-5 month old diabetic mice with reduced circulating levels of LH and in 6-11 month old diabetic mice, of both LH and FSH. In 6-11 month old diabetic mice, testes were characterized by a thickened tunica albuginea, numerous Sertoli cells and the near absence of any spermatogenic cells. The epididymis from these diabetic mice was devoid of spermatozoa.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a Short Feedback of Prolactin on the Tubero‐Infundibular Endings: Differential Effect on the Release of [3 H]Gamma‐Aminobutyric Acid and [3 H]Dopamine from Superfused Median Eminence

Abstract Release experiments were undertaken on the tubero-infundibular terminals of the hypothalamic median eminence. Isolated median eminences were preloaded with [(3) H]y-aminobutyric acid (GABA) or [(3) H]dopamine in such conditions that non-specific uptake was pharmacologically impaired. Each median eminence was continuously superfused with Krebs bicarbonate medium and tritium releases were evoked with high potassium solutions. The evoked release was estimated by measuring the total radioactivity of which actual dopamine and GABA represented more than 60% and 80%, respectively. The experiments were done by applying two successive 5-min pulses of potassium, the second in the presence of prolactin. These stimulations were submaximal: for each, a KCl concentration was chosen that gave about half the maximal response (45 mM for GABA and 30 mM for dopamine); the responses were suppressed by calcium-free medium. Rat prolactin induced a significant increase of dopamine-evoked release in a dose-dependent manner with a maximum (30%) at 25 mug prolactin/ml of medium. Over the same range of concentration a significant but still weak (10%) increase of evoked GABA was observed only with the highest prolactin concentration (25 mug prolactin/ml). At the same concentrations, ovine prolactin induced a markedly reduced effect on dopamine release and had no effect on GABA release. Spontaneous releases of dopamine and GABA were not affected by prolactin. These results show that prolactin enhances acutely and directly, but differently, the evoked release of GABA and dopamine by the median eminence. This differential effect may reflect either a differential regulation or a greater heterogeneity of GABAergic endings. Our data give support for a short feedback exerted by prolactin directly on the tubero-infundibular neurons.

Permeability of Intracranial Blood Vessels to Endogenous Serum Albumin

The blood-brain barrier to endogenous serum albumin labeled with Evans blue was studied by standard fluorescence microscopic techniques in cats. Systematic studies confirm that, except in certain well-known loci (hypothalamic median eminence, subfornical organ, area postrema, etc.), blood vessels within brain tissue are impermeable to endogenous albumin. But studies also demonstrate that in virtually all arteries at the base and over the surface of the brain and brain stem, labeled albumin passes readily through endothelium and the vascular wall to the adventitia. These observations are discussed in the context of current concepts of intracranial vascular permeability and, in terms of general biology, the possible consequences of the permeability to serum albumin of intracranial, extraparenchymal blood vessels on the composition and physiology of cerebrospinal fluid and in the pharmacokinetics of antibiotics, anticonvulsants, and antineoplastic and vasoactive agents.