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Biomedical subjects

W Wuttke

Publications and source records attributed to W Wuttke.

At least 181 records · Page 10Linked to original sources

Hypothalamic and limbic GABA concentrations and turnover rates and glutamate concentrations following induction of hyperprolactinemia in ovariectomized rats.

Hyperprolactinemia was induced by transplantation of pituitaries of donor rats under the kidney capsule of ovariectomized recipient rats. This results in a permanently increased serum prolactin and temporarily suppressed luteinizing hormone (LH) levels. Concentrations of gamma-aminobutyric acid (GABA) and glutamate as well as turnover rates of GABA were determined in micropunches of the nucleus accumbens (ACB), medial preoptic area (MPO), anterior and posterior part of the mediobasal hypothalamus (AMBH and PMBH) and in the mediocortical amygdala (AMY). GABA concentration in the ACB and MPO were reduced in hyperprolactinemic rats. This was significant at day 8. At days 4 to 21 following pituitary transplantation glutamate concentrations were also significantly reduced in the AMY. The most conspicuous changes in GABA turnover rates were observed in the ACB and MPO. In the former structure hyperprolactinemia reduced GABA turnover, while in the latter high prolactin levels increased GABA turnover at day 4. It is concluded that the suppressive effect of hyperprolactinemia on blood LH levels may involve a preoptic GABAergic component and possibly a glutamatergic mechanism in the AMY. Alternatively, the AMY and the ACB may be involved in eliciting the many behavioral effects associated with hyperprolactinemia.

Animals↗

Glutamate in hypothalamic and limbic structures of diestrous, proestrous, ovariectomized and ovariectomized estrogen-treated rats.

Concentrations of glutamic acid were determined in the nucleus accumbens (ACB), medial preoptic area (MPO), anterior and posterior mediobasal hypothalamus (AMBH, PMBH) and mediocortical amygdala (AMY) of diestrous (D), proestrous (P), ovariectomized (OVX) and OVX rats treated with estradiol-benzoate (EB) 12 h and 24 h before decapitation. Significant changes of glutamate concentrations were found in the ACV and PMBH. Glutamate is reduced in OVX when compared to D, P and OVX-EB rats. No significant changes of glutamate concentrations could be detected in the MPO, AMBH, and AMY.

Animals↗

Potassium activity in leech neuropile glial cells changes with external potassium concentration.

The effect of the external K+ concentration on the intracellular K+ activity of neuropile glial cells and of sensory neurons in the central nervous system of the leech (Hirudo medicinalis L.) was determined directly with double-barreled ion-sensitive microelectrodes. As the external K+ concentration was raised, the intracellular K+ activity of the neuropile glial cells increased considerably, and was accompanied by the uptake and/or intracellular synthesis of an, as yet, unidentified substance. In contrast, the intracellular K+ activity of sensory neurons was unchanged when the external K+ concentration was increased. These neurons appeared not to accumulate a second substance.

Animals↗

The Na+-K+ pump in neuropile glial cells of the medicinal leech.

The membrane potential of neuropile glial (NG) cells in the central nervous system of the medicinal leech and the K+ concentration in extracellular spaces (ECS) of the neuropile were measured under various experimental conditions to determine properties of a glial Na+-K+ pump. The ganglia were exposed to K+-free saline thereby loading the NG cells with intracellular Na+. Their membranes hyperpolarized transiently when the K+-free solution was replaced by a bathing medium with normal (= 4 mM) K+ concentration. The hyperpolarization increased in amplitude with time of exposure to K+ -free solution and could be abolished by ouabain or by replacing Na+ with Li+. The transient membrane hyperpolarization could not be attributed to K+ depletion in the ECS of the neuropile or to changes in membrane input conductance. In a (bathing) medium containing 5 X 10(-4) M ouabain, the K+ concentration in the ECS increased transiently, and the NG cell membrane depolarized rapidly. This short-term depolarization (duration 2-3 min) was followed by a second long-term depolarization (duration 15 min) of the NG cell membrane, which reached a steady-state 20 min after ouabain application. In a bathing medium with elevated external K+ concentrations, the amplitude of the membrane depolarization was enhanced by ouabain. This depolarizing ouabain effect was a result of K+ accumulation in the ECS. We conclude that the Na+-K+ pump does not contribute directly to the resting membrane potential of NG cells and is not directly involved in K+ homeostasis at the cellular level.

Animals↗

Involvement of preoptic-anterior hypothalamic GABA neurons in the regulation of pituitary LH and prolactin release.

The effects of intraventricular injections of the highly specific gamma-amino-butyric acid (GABA) agonist muscimol (5 nmol/animal) on blood LH and prolactin levels were measured in ovariectomized (ovx) and in ovx estrogen-progesterone (OEP) primed rats. While the drug stimulated pituitary prolactin release in both experimental groups, pituitary LH release was significantly inhibited in the ovx animals. Muscimol was without any effect on LH levels in ovx-OEP primed rats. Bilateral implantation of tubes containing a muscimol-mannitol mixture into the medial preoptic/anterior hypothalamic (MPO/AH) area abolished pulsatile LH release whereas blood prolactin values were elevated. The intraventricular injection of GABA (8 mumol) also reduced LH and increased prolactin levels in the blood. Measurements of catecholamine turnover rates in the MPO/AH and in the mediobasal hypothalamus (MBH) yielded reduced preoptic but unchanged hypothalamic norepinephrine (NE) and stimulated hypothalamic dopamine (DA) turnover. In view of the well known stimulatory involvement of the NE system in the mechanism of pulsatile LH release and the inhibitory effect of GABA and its agonist muscimol on pulsatile LH release, it is suggested that GABA inhibits NE release in the MPO/AH by the mechanism of presynaptic inhibition. The observation that muscimol is unable to suppress LH release in vox OEP-primed rats may indicate that those estrogen receptive neurons in the MPO/AH which mediate the negative feedback action of the steroid may use GABA as neurotransmitter and that they are the neurons which inhibit NE release. The inhibitory effect of locally implanted muscimol into the MPO/AH also supports this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dopamine-inhibited release of prolactin and intermediate lobe-POMC-peptides: different modulation by opioids.

Primary monolayer cultures of anterior or intermediate lobe (IL) cells from rat pituitaries were grown in microtiter plates, and the test substances were added after 5 days. The hormones were measured by RIAs for rat prolactin, -MSH, ACTH and beta-endorphin/beta-LPH. The dopamine (DA) inhibition of prolactin secretion was attenuated by addition of equimolar (10(-7), 10(-6)M) concentration of beta-endorphin. Furthermore, the DA effect was blocked, when the beta-endorphin-release of anterior pituitary cells was stimulated by vasopressin. In contrast, the DA induced inhibition of hormone-release of IL-cells (e.g. -MSH, ACTH and beta-endorphin) was not influenced by addition of opioids. Our results indicate, that under certain conditions (e.g. stress) the stimulated secretion of prolactin could be mediated partially by a direct action of pituitary beta-endorphin at the lactotroph. On the other hand, we found no indication for a modulation of the dopamine-induced inhibition of IL-peptides by opioids.

Adrenocorticotropic Hormone↗

Catecholestrogens affect catecholamine turnover rates in the anterior part of the mediobasal hypothalamus and medial preoptic area in the male and female castrated rat.

To study the interactions of catecholestrogens with the catecholamine system we estimated the catecholamine concentrations and turnover rates in the anterior part of the mediobasal hypothalamus (AMBH) and medial preoptic area (MPO) following 2-hydroxyestradiol-17 beta (2-OHE2) or 2-hydroxyestrone (2-HOE1) treatment in castrated male and female rats. Serum concentrations of LH and prolactin were also measured. The turnover rates of catecholamines were calculated by monitoring the catecholamine loss 1 h after blocking the catecholamine synthesis with alpha-methyl-p-tyrosine. Dopamine, epinephrine and norepinephrine concentrations were measured by a radioenzymatic assay. In males, 2-OHE2 (50 micrograms/kg) and 2-OHE1 (50 micrograms/kg) resulted in decreased serum LH values (p less than 0.05) 4 and 5 h after treatment. None of these 2-hydroxylated estrogens were able to alter serum prolactin levels significantly. There was a decline in epinephrine and norepinephrine concentrations in the AMBH. The greatest change in catecholamine turnover rates in response to catecholestrogen treatment also occurred in the AMBH. 2-OHE2 and 2-OHE1 reduced turnover rates of dopamine, norepinephrine and epinephrine in the AMBH. Only the dopamine turnover rate was affected in the MPO, where it increased following 2-OHE2 treatment. In females, only 2-OHE2 (50 micrograms/kg) was effective in decreasing serum LH (p less than 0.05) and increasing prolactin (p less than 0.01) levels. Dopamine and epinephrine concentrations as well as their turnover rates declined in the AMBH after treatment with catecholestrogens. The concentration and turnover rate of epinephrine also decreased in the MPO. There was no significant change in norepinephrine concentration or turnover rate. It is suggested that 2-hydroxyestrogens are possibly involved in mechanisms which are inhibitory to LH secretion and stimulatory to prolactin release. These actions appear to be partly mediated by catecholamines.

Animals↗

Involvement of GABA in the feedback action of estradiol on gonadotropin and prolactin release: hypothalamic GABA and catecholamine turnover rates.

The concentrations and turnover rates of norepinephrine (NE), dopamine (DA) and gamma-aminobutyric acid (GABA) were measured in discrete brain areas of diestrous (D), proestrous (P), ovariectomized (OVX) and ovariectomized rats treated with estradiol-benzoate (EB) 12 or 24 h before decapitation. The turnover of NE in the medial preoptic area (MPO) correlates well with plasma LH levels under all endocrine conditions showing high NE turnover in P and OVX and low NE turnover in D and OVX-EB animals. The DA turnover shows no hormone-dependent changes in the MPO. In those animals where estrogens exert no (OVX) or a negative feedback action (D, OVX-EB) on LH the GABA turnover correlates inversely with LH and preoptic NE turnover showing low GABA turnover values in OVX and high values in D and OVX-EB. For P animals the inverse correlation cannot be confirmed. It is concluded that GABA mediates the negative feedback action of estrogens to LH-RH perikarya located in the MPO. GABA might act by presynaptic inhibition of NE axon terminals. This hypothesis is supported by morphological findings which indicate that axon terminals in the MPO are in close contact without separating glial lamellae. In the anterior mediobasal hypothalamus (AMBH) NE turnover correlates best with serum prolactin levels being high in P and OVX animals 24 h after EB treatment. The DA turnover is increased in OVX rats 24 h after EB. It is not yet clear if this increase might be a consequence of the elevated prolactin levels. GABA turnover in the AMBH shows no significant changes. GABA concentrations and turnover rates were also determined in the mediocortical amygdala where estrogen receptors have been reported and in the nucleus accumbens. No significant changes could be observed in these regions.

Animals↗

In vivo GABA release from the medial preoptic area of diestrous and ovariectomized rats.

The push-pull cannula technique was used to examine the endogenous release of GABA from the medial preoptic area (MPO) of unanesthetized rats. In diestrous females the mean resting release of GABA was 27.1 +/- 2.0 pmol/min. GABA release was significantly elevated by increasing the potassium concentration in the perfusion solution to 50 mM, whereas it was dramatically inhibited by mercaptoproprionic acid (1.0 mM), a glutamic acid decarboxylase inhibitor. A comparison between diestrous females and chronically castrated animals indicated that endogenous GABA release in OVX animals was only 60-70% of that in diestrous animals. A model for the presynaptic inhibition of NE by estrogen receptive GABAergic neurons in the MPO is proposed.

Animals↗

Changes in physiological, EEG and psychological parameters in women during the spontaneous menstrual cycle and following oral contraceptives.

In a controlled cross-over design study performed with 14 female subjects, serum hormone levels, the EEG and a number of performance tests were recorded during spontaneous and oral contraceptive-controlled menstrual cycles. The mean alpha-frequency showed cyclic changes, i.e. slower alpha-waves during the follicular phase and faster alpha-waves during the luteal phase. Smaller cycle stage-dependent differences in the power of the theta- and beta-bands also were noted. An increase in several performance task scores was noted during the periovulatory period, whereas lowest performance scores were recorded during the late luteal and early menstrual phases. No such effects were observed in the same subjects while they were taking oral contraceptives. These results demonstrate that the gross electrical activity of the brain changes in a parallel with changed hormone levels. The changes in performance tests coincide with increasing or decreasing alpha activities in the EEG. The common underlying mechanism may be an activation of central nervous system monoaminergic pathways which are known to be involved in steroid feedback.

Adolescent↗

Release and synthesis rates of catecholamines in hypothalamic, limbic and midbrain structures following intraventricular injection of beta-endorphin in male rats.

Serum hormone levels and turnover rates of dopamine (DA), norepinephrine (NE) and epinephrine (E) in tissue of pontine midbrain, limbic caudate, and hypothalamic structures were measured following intraventricular injection of 20 microgram beta-endorphin. Turnover of DA was increased in the locus coeruleus and in structures innervated by the nigrostriatal and mesolimbic DA systems while it decreased in the posterior hypothalamus. The NE turnover was reduced in the locus coeruleus and posterior mediobasal hypothalamus. In all tissues examined, beta-endorphin treatment had no significant effect on E turnover. Serum levels of prolactin and corticosterone increased following beta-endorphin treatment whereas LH, FSH and TSH levels decreased. The observed effects of beta-endorphin on preoptic and hypothalamic DA and NE turnover rates may explain these hormonal changes. The reduced NE turnover in the locus coeruleus may be induced by increased DA turnover. The observation, that NE turnover in structures innervated by locus coeruleus neurons may go in different direction suggest that NE turnover is regulated independently from the activity of locus coeruleus neurons, hence that the regulation must occur at the terminals by a direct or indirect interaction with endorphinergic neurons.

Animals↗

Puberty of female rats may in part be explained by decreased hypothalamic dopamine receptor sensitivity.

Dopamine (DA)-stimulated adenylate cyclase activity in the hypothalamus and preoptic area is highest at day 20 after birth and declines gradually to reach adult values at the time of puberty. Previously it was shown that serum prolactin levels and hypothalamic DA turnover show an inverse pattern. It is suggested that increasing prolactin levels stimulate DA turnover which results in inhibition of luteinizing hormone (LH) release. The constantly high DA turnover at later prepuberal ages desensitizes DA receptors which gradually relieves the inhibitory action of DA on LH release.

Adenylyl Cyclases↗