Effects of insulin-like growth factor-1 on luteinizing hormone secretion in sheep

Liver dysfunction often occurs during chemotherapy for AML, but the etiologies are many and varied. To determine liver dysfunction that is not related to HCV, liver function during intense therapy for one week after complete remission was studied in eight patients not infected with HCV (38 courses) and six HCV-infected patients (19 courses) with AML. There were remarkable differences in changes of ALT levels among HCV-infected patients. ALT level changes among patients not infected with HCV were similar. Changes in mean serum ALT levels in HCV-infected patients occurred at higher serum levels as compared with those in patients not infected with HCV. The mean serum ALT levels in patients not infected with HCV significantly increased at one week (45 +/- 5 IU/l) and further increased at two (58 +/- 8 IU/l) and three weeks (57 +/- 5 IU/l) as compared with pretreatment levels (24 +/- 21 IU/l) (p < 0.001, p < 0.001, p < 0.0001, respectively). ALT levels returned to normal at four weeks. During 31 of 38 courses (81.6%) in patients not infected with HCV, febrile episodes occurred at three weeks. The mean serum ALT levels in patients with febrile episodes were significantly higher than those in patients without febrile episodes at three weeks, and serum ALT levels at three weeks showed a significant positive correlation with CRP levels at three weeks. These findings indicate that liver dysfunction during chemotherapy for AML is due to hepatocellular injury, and infection or inflammatory cytokine induced by infection results in the worsening of the liver dysfunction.     

Day-night changes in c-fos expression in the fetal sheep suprachiasmatic nucleus at late gestation

The suprachiasmatic nucleus (SCN) is a circadian oscillator in mammals and shows day-night changes in metabolic activity. To investigate whether the fetal sheep SCN behaves as a circadian oscillator, day-night changes in c-fos expression, a marker of neuronal activity, were measured. Eight fetal sheep were sacrificed at 135 days gestation--four at day-time (1200 hours) and four at night-time (2400 hours). Fetal brains were fixed, removed and cut in 40-microns serial coronal sections. Alternate sections were incubated with anti-Fos antibody (1:500) and Fos expression was revealed with extra-avidin-peroxidase and 3,3'-diaminobenzidine or stained with cresyl violet. The number of Fos-immunoreactive (Fos-ir) neurons per mm2 in the rostral, intermediate and caudal regions of the fetal sheep SCN was counted. Fetuses sacrificed in the day-time showed a higher number of Fos-ir neurons per mm2 (mean +/- s.e.; 516.7 +/- 60.1) in the three regions of the SCN than fetuses sacrificed at night-time (140.5 +/- 21.8). In addition, at night-time Fos-ir neurons were mainly localized to the ventrolateral area of the SCN. These findings demonstrate day-night changes in molecular activity consistent with the presence of a circadian oscillator in the fetal sheep SCN.     

Serotonin stimulates corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats

To examine the direct effects of serotonin (5-HT) on the release and synthesis of corticotropin-releasing factor (CRF) in the hypothalamic paraventricular nucleus (PVN), 5-HT was microinjected just onto the bilateral PVN of conscious rats. Plasma adrenocorticotropic hormone (ACTH) levels peaked at 30 min and returned to the basal levels in 90 min. Northern blot analysis revealed that the CRF messenger RNA (mRNA) level in the PVN as well as the proopiomelanocortin mRNA level in the anterior pituitary significantly increased 120 min after the 5-HT injections (50-250 nmol/side). Pretreatment with intracerebroventricular (i.c.v.) injection of pindobind 5-HT1A (5 nmol) or LY-278584 (500 nmol) completely abolished the 5-HT-induced ACTH response, whereas LY-53857 (100 nmol) was without effect. These results suggest that 5-HT stimulates CRF release, which has interactions with 5-HT1A and 5-HT3 receptors on CRF neurons in the PVN, and activates CRF synthesis in conscious rats.     

Interaction between hypothalamic dopaminergic and opioidergic systems in the photoperiodic regulation of pulsatile luteinizing hormone secretion in sheep

Previous studies in sheep have shown that whereas the inhibitory effects of dopamine (DA) systems on GnRH/gonadotrophin secretion are readily detectable during the sexually inactive phase under long days (LD), the suppressive effects of endogenous opioid peptide (EOP) systems are most evident during the sexually active phase under short days (SD). The hypothesis proposed in this study is that inhibitory DA pathways interact with EOP neurons to regulate GnRH/gonadotropin secretion in sheep and that photoperiod modulates this interaction to relay its effect on the seasonal reproductive cycle. To test this hypothesis, the effects of a DA agonist (bromocriptine) or of a DA antagonist (sulpiride) on the pulsatile LH response to an opioid antagonist (naloxone) were evaluated in sexually active Soay rams exposed to SD, and then reassessed when sexually inactive under LD. The experimental design comprised six treatments: 1) control (vehicle); 2) bromocriptine; 3) sulpiride; 4) naloxone; 5) pretreatment with bromocriptine followed by naloxone; 6) pretreatment with sulpiride followed by naloxone. Under SD, when DA pathways are thought to be quiescent and EOP systems active, bromocriptine suppressed pulsatile LH secretion (P < 0.01), whereas sulpiride had no effect. Under this photoperiod, naloxone induced a conspicuous stimulation of episodic LH release (P < 0.01). This effect was prevented by pretreatment with bromocriptine (P < 0.01), but was not affected by pretreatment with sulpiride. Conversely, under LD, when the activity of DA pathways is thought to be increased and that of EOP systems reduced, bromocriptine was without effect, whereas sulpiride evoked a mild increase in LH pulse frequency (P < 0.05). Under this photoperiod, naloxone induced a smaller stimulation than under SD. This effect was again blocked by pretreatment with bromocriptine but, in contrast to SD, markedly enhanced by pretreatment with sulpiride (P < 0.01). Particularly relevant was that the DA agonist blocked the stimulatory effects of the EOP antagonist under SD, and that the DA antagonist enhanced the effects of the EOP antagonist only under LD. These results are consistent with the hypothesis proposing that, in sheep, DA pathways have a predominant inhibitory effect on both GnRH and EOP neurons, and that changes in day length modulate the interplay between DA and EOP systems as part of the mechanisms involved in the photoperiodic control of the seasonal reproductive cycle.     

Rhythmicity of luteinizing hormone secretion expressed in vitro

In the present study we explored the possibility that the pituitary functions as an autonomous clock and is capable of generating rhythms of luteinizing hormone (LH) release independently of hypothalamic control. Pituitaries from estrous or diestrous day 1 female mice were perifused separately with Medium-199. Effluent samples were collected at 10-min intervals and assayed for LH levels. Fourier analysis and curve-fit analysis served to elucidate the presence of prominent periods whose significance was then determined by best-fit cosinor. The latter method was used to determine additional parameters for the significant rhythm. All perifused pituitaries exhibited LH release patterns that were composed of significantly long ultradian rhythms (approximately 16 and 8 h, p < 0.001). Continuous stimulation with gonadotropin-releasing hormone (GnRH) or estradiol did not alter the periods of the observed rhythms but affected other rhythm parameters. Gonadotropin-releasing hormone increased the mesor of the rhythm and estradiol increased the amplitude. The results indicate that pituitary gonadotropes are capable of producing rhythms of LH release for a long duration in vitro, in the absence of hypothalamic control. Both GnRH and estradiol affect different rhythm parameters but do not change the periods of these rhythms.     

Levels of corticotropin-releasing hormone messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus and proopiomelanocortin mRNA in the anterior pituitary during late gestation in fetal sheep

CRH regulates POMC gene expression and subsequent ACTH biosynthesis and release. In sheep, the preterm rise in fetal plasma ACTH commences at approximately 125 days gestation (dGA; 147 dGA = term), preceding the initiation of adrenocortical steroidogenesis. We hypothesized that an increase in CRH expression in the hypothalamic paraventricular nucleus (PVN) and POMC expression in the anterior pituitary in the late gestation sheep fetus may precede adrenal cortex maturation. Fetal sheep were obtained at 105-107 (n = 4), 128-130 (n = 5), and 138-140 (n = 4) dGA. Hypothalami were cryosectioned and subjected to in situ hybridization for ovine CRH mRNA. In all dGA groups, expression of CRH mRNA was observed throughout the rostrocaudal extent of the fetal PVN. The midrostral region of the fetal PVN where the dorsal and ventral divisions of the rostral PVN merge to form a single structure was selected for quantification. The number of copies of CRH probe hybridized per micron 3 were determined to estimate the quantity of hybridized CRH mRNA; the mean estimated CRH mRNA copy number per micron 3 midrostral PVN were 0.064 +/- 0.012 (105-107 dGA), 0.237 +/- 0.048 (128-130 dGA), and 0.108 +/- 0.034 (138-140 dGA; mean +/- SEM copies per micron 3 PVN). CRH mRNA signal significantly increased between 105-107 and 128-130 dGA (P < or = 0.05); 138-140 dGA levels of mRNA were not different from either 105-107 or 128-140 dGA levels. Regional variation in CRH mRNA levels were observed within the midrostral PVN between groups; at 138-140 dGA, a population of lateral midrostral PVN neurons maintain CRH mRNA levels greater than 105-107 dGA (P < 0.05), similar to those at 128-130 dGA. Fetal anterior pituitary RNA was subjected to Northern analysis for POMC mRNA. POMC mRNA levels in fetal anterior pituitaries were 14.1 +/- 2.2 (105-107 dGA), 28.9 +/- 10.9 (128-130 dGA), and 43.2 +/- 6 (138-140 dGA; mean +/- SEM arbitrary units). A significant increase (P < or = 0.05) was observed at 138-140 dGA compared to levels at 105-107 dGA. We conclude CRH mRNA levels in the fetal PVN increase coincident with increased POMC gene expression and the late gestation rise in fetal plasma ACTH. We speculate that a neuroendocrine stimulus at the fetal PVN may precipitate increased levels of CRH mRNA, initiating the maturation of the fetal hypothalamic-hypophyseal-adrenal axis, thus inducing the events of labor and delivery in sheep.     

Hypothalamic sites of action for testosterone, dihydrotestosterone, and estrogen in the regulation of luteinizing hormone secretion in male sheep

Testosterone (T) inhibits LH secretion partly by acting at unknown sites within the brain to inhibit GnRH secretion. We tested the hypothesis that the preoptic area (POA) and arcuate-ventromedial region (ARC/VMR), areas rich in androgen and estrogen (E) receptors, are neural sites at which T and the T metabolites, dihydrotestosterone (DHT) and estrogen (E), act to suppress LH secretion. Bilateral guide cannulae were surgically implanted into either the POA or ARC/VMR of castrated male sheep. Experiments were conducted under a long day photoperiod to maximize the inhibitory effect of the steroids. In Exp 1, all sheep (n = 6/site) sequentially received bilateral implants of cholesterol (CHOL), T, or E at each site. Jugular blood samples were taken at 10-min intervals for 4 h both immediately before implant insertion and 5 days later. In Exp 2, all sheep (n = 6/site) sequentially received bilateral implants of CHOL, DHT, or E at each site according to a latin square design. Blood samples were taken before and 7 days after implant insertion. In Exp 3, which followed the same design as Exp 2, implants of E, T, or DHT were placed only in the ARC/VMR. In the final experiment, the effects of T and CHOL implants in the ARC/VMR were compared. Neither T, DHT, nor CHOL implants at either site affected LH secretion. In contrast, E treatment in the ARC/VMR suppressed mean plasma LH levels (P < 0.01), primarily due to an increase in interpulse interval (P < 0.01). Estrogen implants in the POA caused a small, but nonsignificant (P > 0.05), decrease in mean LH levels in the first experiment and an increase in LH interpulse interval (P < 0.05) in the second experiment. These results suggest that the ARC/VMR and possibly the POA are sites at which E acts to reduce GnRH secretion in male sheep.     

Seasonal changes in pituitary function: amplification of midfollicular luteinizing hormone secretion during the dark season

OBJECTIVE: To analyze the effect of season on the pulsatility of gonadotropin secretion in women living in an area with a large annual variability in daylight length. DESIGN: A prospective study. Pulse studies were carried out in each subject during both the dark and light season. SETTING: The gynecologic endocrine research unit of the University Central Hospital of Oulu. PARTICIPANTS: Eleven ovulatory, healthy women volunteering for the study. INTERVENTIONS: Serum samples were collected at 10-minute intervals for 6 hours on days 7 to 9 of the cycle. MAIN OUTCOME MEASURES: Serum LH and FSH concentrations were measured and the data were analyzed with an algorithm computer-based program. RESULTS: The mean area of LH pulses analyzed was significantly higher during the dark season than the light season (49.1 +/- 3.1 versus 38.5 +/- 1.7 mIU/mL; conversion factor to SI unit, 1.00), while in the amplitude (1.9 +/- 0.1 versus 1.8 +/- 0.1 mIU/mL), number of pulses (5.2 +/- 0.3 versus 4.4 +/- 0.6), and the mean level (9.6 +/- 0.5 versus 9.4 +/- 0.9 mIU/mL) the difference did not reach statistical significance. The number (5.2 +/- 0.5 versus 5.2 +/- 0.4,), amplitude (1.0 +/- 0.05 versus 1.1 +/- 0.07 mIU/mL; conversion factor to SI unit, 1.00), area (29.9 +/- 2.4 versus 29.6 +/- 3.1 mIU/mL), and the mean level of FSH (5.4 +/- 0.6 versus 6.0 +/- 0.8 mIU/mL) during the dark and light seasons were identical, showing no seasonal variability. CONCLUSIONS: The results indicate increased pituitary LH secretion in the midfollicular phase during the dark season that may be related to increased melatonin secretion and decreased ovarian activity at this time of the year.     

Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat

Intraperitoneal (i.p.) administration of sulfated CCK octapeptide (CCK-8S) has been shown to induce changes in neuronal activity in the nucleus of the solitary tract (NTS) and area postrema (AP), sensory parts of the dorsal vagal complex (DVC), and in the paraventricular nucleus of the hypothalamus (PVN), as determined by activation of c-fos expression. Whether peripheral CCK influences neuronal activity in the locus coeruleus (LC)/subcoeruleus nucleus (SC) was investigated in awake rats at intraperitoneal (i.p.) injection of CCK-8S by c-Fos immunohistochemistry. CCK-8S i.p. (25, 50, and 100 micrograms/kg, respectively) dose-dependently increased the average number of c-Fos-LI-positive cells/section in the LC/SC by the factor 5.9, 8.2, and 11.7, respectively. Pretreatment with the CCK-A receptor antagonist MK-329 (devazepide; 1 mg/kg and 2 mg/kg i.p.) reduced the CCK-induced increase in c-fos expression in the LC/SC by 54% and 75%, respectively; the CCK-B receptor antagonist L-365,260 had no effect. Perivagal capsaicin pretreatment diminished the CCK-induced increase in the number of c-Fos-LI-positive cells in the LC/SC by 65%. In comparison, the CCK-A antagonist devazepide (1 mg/kg and 2 mg/kg i.p.) reduced the increase in c-fos expression by 76% and 88% in the PVN, 69% and 88% in the NTS, 86% and 83%, respectively, in the AP. Capsaicin diminished the CCK-induced increase in c-Fos-LI-positive cells in the PVN by 64%, in the NTS by 60%, but in the AP only by 25%. Immunostaining against the nuclear antigen c-Fos and the cytoplasmatic antigen tyrosine hydroxylase (TH) showed that 40% of all c-Fos-LI-positive cells in the LC/SC were TH-LI positive at 25 micrograms CCK/kg. The data indicate that CCK-8S i.p. induces modulation of neuronal activity in the LC/SC, DVC and PVN predominantly by peripheral action of CCK-A receptors and capsaicin-sensitive vagal afferents. These findings suggest that the LC/SC is involved in CNS-mediated regulatory influences of peripheral CCK.     

Stimulation of neuropeptide Y overflow in the rat paraventricular nucleus by corticotropin-releasing factor

Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) are present at high concentrations in the hypothalamus where they mediate important endocrine and autonomic functions. Morphological and physiological studies have suggested an interaction between these peptides, and opposing actions of CRF and NPY have been reported on feeding and other behaviors. This study investigated the effect of CRF on NPY release in vivo, measured by push-pull techniques, in the anesthetized rat. Push-pull probes implanted into the paraventricular nucleus of the hypothalamus (PVN) were perfused with modified Ringer solution containing bovine serum albumin at 15 microl/min, and the perfusate was lyophilized prior to NPY radioimmunoassay. NPY overflow from the rat PVN was increased threefold by perfusion of a depolarizing concentration of potassium (50 mmol/L KCl). When CRF was administered into the PVN via the push-pull cannula at 1 or 5 microg/ml, dose-dependent increases in NPY overflow of two- and fivefold were observed (p < 0.05). These increases were abolished by prior intracerebroventricular (i.c.v.) administration of the CRF antagonist [D-Phe12,Nle(21,38),C(alpha)MeLeu32]CRF (12-41) at 1 or 5 microg/microl, respectively. NPY overflow returned promptly to resting levels following CRF administration. In contrast, when CRF was administered by i.c.v. bolus at a similar total dose (2 microg), no significant effect on NPY overflow was observed. These data provide in vivo evidence for an interaction between CRF and NPY at the level of the PVN.     

Corticotropin releasing factor mRNA expression in the hypothalamic paraventricular nucleus and the central nucleus of the amygdala is modulated by repeated acute stress in the immature rat

A new approach to the study of the interaction of amino acid side chains with photoreactive aryl azides was proposed. This approach was based on the drawing together of the reacting groups by the attachment of the reacting compounds to complementary oligonucleotides. Cystamine, histamine, and 1,6-hexamethylenediamine mimicking the cystine, histidine, and lysine residues, respectively, were attached to the 3'-terminal phosphate of the oligonucleotide GGTATCp through a phosphamide bond and used as the targets for photomodification. Derivatives of the oligonucleotide pGATACCAA with the fragment N3C6H4NH- attached directly to its 5'-end by a phosphamide bond or through the spacer -(CH2)nNH- (where n is 2, 4, and 6) were used as photoreagents. Their derivatives containing the same spacer and the N3C6F4CO-NH(CH2)3NH- or 2-N3,5-NO2-C6H3CO-NH(CH2)3NH- residues were also used. The duplexes were photomodified by irradiation with 300-350 nm wavelength light. The maximal yields of the photo-cross-linking were from 22 to 68%. The reagents containing p-azidoaniline residue were found to be the most effective toward the targets. The maximum yields of the photomodification products modeling the side chains of cysteine and lysine were found to vary from 40 to 67% and to depend on the length and the structure of the spacers used. The duplex with the target bearing the imidazole residue (the histidine model) manifested a yield decreased to 25%. This fact was in a good agreement with the data of computer modeling that indicated an unfavorable mutual displacement of the imidazole residue and the photoreactive group.     

The arcuate nucleus is the major source for neuropeptide Y-innervation of thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus

Neuropeptide Y (NPY) immunoreactive (-ir) nerve fibers densely innervate hypophysiotropic TRH perikarya and dendrites in the hypothalamic paraventricular nucleus (PVN). To evaluate the contribution of the arcuate nucleus (Arc) to this innervation, the effect of Arc ablation by neonatal monosodium glutamate (MSG) treatment on the density of NPY-fibers contacting TRH neurons in the PVN was investigated. After the lesioned animals and vehicle-treated controls reached adulthood, the number of contacts between NPY-ir boutons and TRH-ir perikarya in the PVN was determined in double-immunostained sections. In controls, numerous contacts between NPY-ir terminals and TRH perikarya and dendrites were observed, confirming earlier findings. MSG treatment resulted in a marked reduction of the size of the Arc and also the number of NPY-perikarya with a concomitant reduction of 82.4 +/-2.1% in the relative number of NPY terminals contacting TRH perikarya and first order dendrites in the medial parvocellular and periventricular subdivisions of the PVN. In contrast, lesioning of the ascending adrenergic bundle in the brain stem caused no statistically significant change in the number of NPY-terminals in close apposition to hypophysiotropic TRH neurons in the PVN. These data confirm earlier findings that NPY-containing axon terminals innervate TRH neurons in the PVN and further demonstrate a potentially important anatomical relationship between NPY-producing neurons in the Arc and hypophysiotropic TRH neurons.     

Suckling-induced inhibition of luteinizing hormone secretion and follicular development in the early postpartum sow

The endocrine basis of lactational anestrus, the causes of reproductive dysfunction after early weaning, and the relationships among LH, FSH, and prolactin (PRL) secretion and follicular development were evaluated in sows weaned 6 h after farrowing (zero-weaned, n = 8) and in normally lactating sows (n = 9). An irregular, high-frequency episodic-type pattern of LH secretion was present in the early postpartum period, irrespective of treatment, and in a proportion of sows this pattern was associated with a marked elevation of baseline LH concentrations. This pattern of LH secretion was maintained in the zero-weaned sows but LH secretion was inhibited in lactating sows, resulting in a difference (p < 0.05) in mean plasma LH between groups 72-78 h postpartum. There were no differences in FSH between groups in any period of sampling. Variable but elevated plasma PRL was observed in suckled sows but declined (p < 0.05) to basal levels within 12 h of zero-weaning. Follicular development measured at laparotomy or slaughter 96 h postpartum was greater (p < 0.05) in zero-weaned than in control sows. The development of lactational anestrus in the sow therefore requires suckling-induced inhibition of LH secretion by 78 h postpartum. This inhibition of LH release does not appear to be causally related to short-term changes in PRL secretion.     

Contributions of endogenous inhibin and estradiol to the regulation of follicle-stimulating hormone and luteinizing hormone secretion in the pregnant rat

To examine the contributions of endogenous inhibin and estradiol to the regulation of FSH and LH secretion in the pregnant rat, some rats were passively immunized against inhibin and/or estradiol, and others were ovariectomized, on Days 5, 10, 15, and 20 of pregnancy. Ovarian and uterine venous blood was collected separately to confirm the sources of inhibin and steroid hormones during pregnancy. Immunoreactivity of inhibin in the placenta was also examined by RIA. Levels of inhibin in ovarian venous plasma were significantly higher than those in peripheral plasma during pregnancy. No difference was observed between the levels of inhibin in uterine venous plasma and peripheral plasma. No immunoreactivity of inhibin was detected in placental homogenate from rats at Days 10, 15, and 20. FSH secretion significantly increased after immunoneutralization of inhibin during pregnancy. A marked increase in FSH secretion was noted on Days 5 and 20, and the smallest increase was observed on Day 15. Administration of estradiol antiserum (AS) alone did not induce a significant increase in FSH secretion on any day of pregnancy. However, a synergistic effect of estradiol AS and inhibin AS was observed on Day 20. On Days 5, 10, and 20, administration of inhibin AS or estradiol AS induced a significant increase in LH secretion. A synergistic effect of inhibin AS and estradiol AS on LH secretion was observed on Day 5. On Days 5 and 10, significantly high LH secretion was noted in ovariectomized rats as compared with that in rats treated with both inhibin AS and estradiol AS, indicating that other ovarian hormones such as progesterone may be involved in the suppression of LH secretion in these stages of pregnancy. These data indicate that both inhibin and estradiol, predominantly secreted from the ovary, are involved in the regulation of gonadotropin secretion during pregnancy as during the estrous cycle in the rat.     

Inhibition of ovarian follicular development associated with a decrease in luteinizing hormone levels during the estrous cycle of the rat

The orientation of microtubules (MTs) was examined in epidermal cells of azuki bean (Vigna angular is Ohwi et Ohashi) epicotyls. The orientation of MTs adjacent to the outer tangential wall of the cells, which has a crossed polylamellate structure with lamellae of longitudinal cellulose microfibrils alternating with lamellae of transverse cellulose microfibrils, differed from one cell to another. Treatment with an auxin-free solution caused the accumulation of cells with longitudinal MTs and subsequent treatment with a solution that contained auxin resulted in the accumulation of cells with transverse MTs, showing that sequential treatments with auxin-free and auxin-containing solutions can synchronize the reorientation of MTs. The MTs, once reoriented from longitudinal to transverse, returned to longitudinal and then back to transverse once again, the duration of the cycle being about 6h. Gibberellic acid, known to increase the percentage of cells with transverse MTs, promoted reorientation of MTs from longitudinal to transverse and inhibited that from transverse to longitudinal. Cytochalasin D, an agent that disrupts actin filaments, speeded up the reorientation from transverse to longitudinal and slowed down that from longitudinal to transverse. It caused an increase in the percentage of cells with MTs in mixed orientation, and the percentage of such cells was highest when the percentage of cells with longitudinal MTs was decreasing and that of cells with transverse MTs was increasing.     

Priming effect of exogenous oestradiol on luteinizing hormone secretion in prepubertal lambs

Electrophysiological exploration of the facial nerve requires different tests to differetciate the importance of the block, denervation and canal conduction. We must answer five questions: 1) Assessing the degree and the phase of the nerve lesion, 2) Deciding on the advisability of a facial decompression in the early stage of the palsy, 3) Evaluating the prognosis, 4) Choosing the best therapeutic approach, 5) Detecting facial hyperkinesis in an infraclinic period. In order to answer these questions, we select the following methods: 1) Quantified Electroneuronography should be applied as early as the 2nd day after onset, repeated on the 7th and 10th days. Unfortunately this is not always possible for practical reasons. In any case a minimum of two investigations should be performed during the 12 first days. 2) We add Computer EMG in order to control the evolution of the blocked fibers with regard to denervated fibers. 3) Blink reflex and Stapedius reflex are investigated from the 3rd day. After the acute phase of the palsy, recovery is detected by the reappearance of the blink and stapedius reflexes and the evolution of the computed EMG. These tests are sufficient for answering the five questions mentioned above without discomfort for the patient.     

Neuroendocrine mechanism mediating fasting-induced suppression of luteinizing hormone secretion in female rats

Forty-eight hours fasting profoundly suppresses LH secretion in female rats. The following neural pathway mediating fasting-induced suppression of LH secretion has been suggested by a series of experiment: a signal associated with fasting emanating from the upper digestive tract reaches the A2 region in the medulla oblongata via afferent vagal nerve so as to activate the noradrenergic pathway projecting to the hypothalamic paraventricular nucleus (PVN); this results in an increased corticotropin-releasing hormone release to suppress LHRH release and then LH release. The PVN and A2 region of the medulla oblongata are the estrogen feedback sites to activate the above-mentioned neural pathway. The estrogen feedback action on the PVN and A2 region is considered to be due to an increased expression of estrogen receptors in these nuclei after 48-h fasting. The response of gonadal axis during fasting could be due to the changes in some nutrients, such as glucose and free-fatty acids. In this context, malnutrition could be a kind of stress accompanied by an increased feeding behavior and decreased gonadal activity.