LH down-regulates gonadotropin-releasing hormone (GnRH) receptor, but not GnRH, mRNA levels in the rat testis.

The demonstration of an inhibitory effect of gonadotropin-releasing hormone (GnRH) agonists upon steroidogenesis in hypophysectomized rats and the presence of mRNA coding for GnRH and GnRH receptors (GnRH-R) in rat gonads suggests that GnRH can act locally in the gonads. To assess this hypothesis, we investigated the effects of GnRH analogs, gonadotropins and testosterone on the levels of both GnRH and GnRH-R mRNA in the rat testis. Using dot blot hybridization, we measured the mRNA levels 2 to 120 h after the administration of the GnRH agonist, triptorelin. We observed an acute reduction of both GnRH and GnRH-R mRNAs 24 h after the injection (about 38% of control). However, the kinetics for testis GnRH-R mRNA were different from those previously found for pituitary GnRH-R mRNA under the same conditions. Initially, the concentrations of serum LH and FSH peaked, then declined, probably due to the desensitization of the gonadotrope cells. In contrast, the GnRH antagonist, antarelix, after 8 h induced a 2.5-fold increase in GnRH-R mRNA, but not in GnRH mRNA, while gonadotropins levels were reduced. Human recombinant FSH had no significant effect on either GnRH or GnRH-R mRNA levels. Inversely, GnRH-R mRNA levels markedly decreased by 21% of that of control 24 h after hCG injection. Finally, 24 h after testosterone injection, a significant increase in GnRH-R mRNA levels (2.3 fold vs control) was found, but a reduction in the concentration of serum LH, probably by negative feedback on the pituitary, was observed. In contrast, GnRH mRNA levels were not significantly altered following testosterone treatment. Since LH receptors, GnRH-R and testosterone synthesis are colocalized in Leydig cells, our data suggest that LH could inhibit the GnRH-R gene expression or decrease the GnRH-R mRNA stability in the testis. However, this does not exclude the possibility that GnRH analogs could also affect the GnRH-R mRNA levels via direct binding to testicular GnRH-R. In contrast, the regulation of GnRH mRNA levels appeared to be independent of gonadotropins. Taken together, our results suggest a regulation of GnRH and GnRH-R mRNA specific for the testis.

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary.

The identification of gonadal gonadotropin-releasing hormone receptors (GnRH-R) and evidence of direct inhibitory effects of GnRH agonists upon steroidogenesis in adult rat gonads, lend credence to a putative intragonadal role of a locally secreted GnRH or GnRH-like peptide. Using reverse transcription-polymerase chain reaction followed by Southern blot hybridization and sequencing, we identified, both in the ovary and in the testis of fetal and adult rats, a fully processed GnRH messenger RNA (mRNA), the sequence of which, in adult testis, was identical to that found in the hypothalamus. We also detected in the testis, but not in the ovary, a transcript containing the first intron. The ontogeny of GnRH and GnRH-R gene expression was studied in rat gonads from 14.5 to 21.5 days post-coitum (dpc), using dot blot hybridization of total RNA. During this period, the levels of cyclophilin mRNA normalized to total RNA remained unchanged. Thus, we used cyclophilin as an internal standard. GnRH mRNA was detected in the ovary at 18.5 dpc, four days later than in the testis, and similar levels were found in both sexes at birth. GnRH-R mRNA was present at 14.5 dpc in the testis and at 15.5 dpc in the ovary, with the levels at 21.5 dpc being 2.4 times higher in the testis than in the ovary. GnRH and GnRH-R mRNA levels increased in both sexes in late fetal development, but this increase appeared two days sooner in the ovary compared with the testis, thus supporting the hypothesis that expression of the GnRH and GnRH-R genes is regulated in a sex-dependent manner during fetal development. In all cases, expression of GnRH and GnRH-R preceded gonadotropin receptors in the gonads and initiation of gonadotropin secretion by the pituitary.

Auditory continuity and loudness computation.

Sequences composed of alternating bursts of different levels with no silences separating them can give rise to a perception of a continuous sound upon which is superimposed an intermittent stream. These experiments sought to determine how the perceived loudness of the intermittent stream depends on the level difference between higher-level and lower-level bursts in the sequence in cases in which continuity is either heard or not heard. In the main experiment, listeners were asked to adjust the level of continuous or intermittent comparison sequences to match the loudness of components that appeared to be either continuous or intermittent in an alternating-level reference sequence, thus urging them to focus on the two-stream percept. Loudness matches of continuous comparison stimulus were close to physical levels of the lower-level bursts, whereas matches of the intermittent comparison stimulus were well below the physical levels of higher-level bursts. These results are discussed in terms of Bregman's [Auditory Scene Analysis (MIT, Cambridge, MA, 1990)] "old-plus-new" hypothesis: The loudness of the intermittent stream should result from the subtraction of the lower level from the higher level under the assumption that the higher-level burst represents a simultaneous mixture of sounds including the continuation of the lower-level burst. Additional experiments verified that, in the absence of the continuity phenomenon, matched levels were very close to the physical levels and that matches to fixed-level continuous and intermittent sequences were precise. The matching results from the main experiment support predictions of neither classical loudness models that do not take auditory organization processes into account nor schema-based models that presume a selection of information from the higher-level burst that does not affect the perceptual content of this burst. The matched levels fell between predictions of models based on subtraction of acoustic pressure and acoustic power, but were very different from subtraction of loudness measured in sones, suggesting that loudness is computed subsequent to auditory organization processes.

Perceptual attenuation of nonfocused auditory streams.

The aim of this study was to measure the perceptual attenuation, measured in decibels, resulting from the focusing of attention on one stream within a multistream auditory sequence. The intensity of a nonfocused stream was increased until the accuracy of detecting a temporal irregularity in this stream was the same as in a focused stream. Eight subjects were required to detect a temporal irregularity created by delaying or advancing one tone which could be situated in one of three temporally regular streams played simultaneously to create a multistream sequence. The three streams differed in tempo and frequency. Subjects' attention was focused on one of the streams by preceding the multistream sequence with one of the single streams (a cue). We first established the size of temporal irregularity detected at a 90% level in cued streams, confirming that subjects were able to focus on one particular stream. Second, an irregularity of this size was not detected above chance level in noncued streams, demonstrating that listeners focus only on the cued stream. Third, for 5 subjects, a 15-dB increase in the level of one of the noncued streams was necessary to bring detection up to that found in the cued streams. This gain provides an equivalent measure of the perceptual attenuation of nonfocused streams. For 3 other subjects, detection in the noncued stream remained at chance performance whatever the level. For all subjects, detection in the cued stream decreased slightly as the level of the noncued stream increased. We conclude that the attenuation of nonfocused auditory streams can attain as much as 15 dB, at least for some subjects.

Auditory attentional bandwidth: effect of level and frequency range.

This study investigated the relations between theoretical auditory filters and "attentional filters" observed when measuring the detectability in noise of tones of expected or unexpected (probe) frequency. The effect of the level of the noise and the frequency range (narrow or wide) of the probes was assessed. For each 2IFC trial, a tone of the expected target frequency was presented as a cue preceding the two observation intervals--the signal was more often the expected than an unexpected frequency. For the narrow frequency range of probe frequencies, increasing the masker level resulted in a broadening of the probe-signal contour (percent correct as a function of probe frequency); however, detection was significantly better only for probe frequencies farthest from the target frequency. For the wide range of probe frequencies, the percentage of correct detections depended less systematically on masker level; however, detection was better and the attentional band wider than in the narrow frequency range. The results suggest that attentional focusing does not simply reflect auditory filtering: A more central and adaptive process may operate from the outputs of adjacent or more distant auditory filters.

New data on the short-term effects of tone exposure.

Three experiments studied the short-term effects of moderate- and high-level tone exposures on threshold and loudness. Experiment 1 measured temporary threshold and loudness shifts (TTS and TLS) due to a 1000-Hz exposure at a moderate level (65 dB SPL) as a function of exposure duration. Whereas there was no significant TTS, TLS was as high as 11 dB and recovered rapidly. TLS was significantly larger for the highest test levels. TTS and TLS were practically independent of exposure duration. Experiment 2 measured TTS and TLS as a function of test frequency following exposures to 500-, 1000-, or 3000-Hz tones at 65 dB SPL. The frequency patterns of TLS were established at test levels of 20-60 phons. TLS and TTS had similar frequency patterns with a maximum at the exposure frequency, but TLS patterns were higher and more extended than those of TTS. In experiment 3, subjects were exposed to a 1000-Hz tone at a high level (90 dB SPL). Frequency patterns for TTS or TLS at a 60-dB test level were measured repeatedly during 5 1/2 min after the end of exposure. Two short-term effects were observed immediately after the exposure: (1) a slight TTS (4.5 dB) at the exposure frequency which disappeared 2 to 3 min later; and (2) a large TLS (9 dB) which extended over the whole range of test frequencies, recovered rapidly, and had disappeared by 330 s after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Tempo sensitivity in auditory sequences: evidence for a multiple-look model.

Differential thresholds for tempi (with interonset intervals ranging from 100 to 1,500 msec) were measured using an adaptive 2IFC paradigm for several types of auditory sequences. In Experiment 1, the number of intervals in an isochronous sequence was varied to compare the sensitivity for single intervals with that for sequences of two to six intervals. Mean relative just noticeable differences (JNDs) decreased as the number of intervals increased (single intervals = 6%, two intervals = 4%, four intervals = 3.2%, six intervals = 3%) and were optimal at intermediate tempi for both sequences and single intervals (as low as 1.5% in the range between 300 and 800 msec). In Experiment 2, the sensitivity for different types of irregular sequences was studied. Globally, JNDs for irregular sequences were of an intermediate level between that observed for single intervals and that observed for regular sequences. However, the closer a sequence was to regularity, the lower its relative JND. Experiment 3 demonstrated that musicians were more sensitive than nonmusicians to changes in tempo, and this was true for single intervals and for regular and irregular sequences, demonstrating the role of training on these abilities. The results are discussed in terms of possible underlying mechanisms, in particular those providing a mental representation of the mean and dispersion of successive interval durations.

Temporary threshold and loudness shifts: frequency patterns and correlations.

Two experiments studied the frequency pattern of TLS (temporary loudness shift) as a function of the level and frequency of the fatiguing sound. In experiment 1, the fatiguing tones were intermittent 375-, 1500-, or 3000-Hz tones (10 s on/10 s off) at 75, 80, 85, 90, or 95 dB SPL. The TLS patterns were established for a continuous, 60-phon test tone at different frequencies presented simultaneously with the intermittent fatiguing tone. In experiment 2, a 1000-Hz exposure tone with an intermittency of 10 s on/20 s off was used with a continuous 60-dB test tone at different frequencies. In both experiments, the total exposure duration was 60 s; TLS was measured 5 s after the exposure ended. For the lowest two exposure levels, the TLS pattern had one peak centered on the exposure frequency. As the exposure level increased, a two-peak pattern became evident, with the second peak at higher test frequencies. This finding could be interpreted as psychoacoustical evidence for the double (passive and active) mode of displacement of the basilar membrane. In experiment 2, a TTS (temporary threshold shift) measurement after exposure to a 45-min, 1000-Hz tone at 90 dB was added to the TLS sessions. The correlations between maximum TTS after a 45-min exposure and the TLS obtained after a 60-s exposure were calculated for each of the exposure levels and test frequencies used in TLS measurements. The correlation reached as high as 0.9 for TLSs measured at 1120 Hz after a 90-dB exposure; it was smaller but significant for TLSs at the exposure frequency. Despite these correlations, differences in the overall patterns of TTS and TLS suggest that they stem from two different mechanisms.

Loudness adaptation in children.

Simple loudness adaptation was measured for a steady tone presented alone at 10 dB SL; contralaterally induced adaptation was measured for a steady tone in one ear accompanied by an intermittent tone in the contralateral ear; ipsilaterally induced adaptation was measured for a tone increased intermittently by 15 dB. The method of successive magnitude estimation revealed no differences between 12 adults and 36 children from 9 to 14 years of age in the amounts of adaptation over a 3-min exposure. A second set of experiments with a new group of 20 adults and 20 children used a Békésy tracking procedure to reach similar results. Unlike Kärjä [Acta Oto-Laryngol 1968; (suppl)241:1-56], who found significant adaptation in only 5 of 29 children and much adaptation in most adults, we found considerable adaptation in children as well as in adults.

Frequency selectivity in loudness adaptation and auditory fatigue.

An intermittent monaural tone may induce a decline in the loudness of a continuous tone presented to the same ear [Canévet et al., Br. J. Audiol. 17, 49-57 (1983)]. Two experiments studied the frequency selectivity of loudness adaptation induced in this manner. The method of successive magnitude estimations was used to measure the loudness of a monaural 84-s test tone before and after a single presentation of a 24-s inducer tone in the same ear. The first experiment shows that, for an inducing tone (500, 1000, or 3000 Hz) approximately 15 dB more intense than a test tone set to one of 21 different frequencies, adaptation is greatest when the two tones have the same frequency; with increasing difference between the test-tone and inducer frequencies, adaptation progressively declines. The second experiment measured frequency selectivity in the loudness reduction caused by a 1000-Hz inducer as a function of its level. As inducer level went from 75 to 95 dB (with test tone constant at 60 phons), selectivity passes progressively from the type seen in short-term or low-level fatigue (maximal for the 1000-Hz test tone) to a type seen in long-term or high-level fatigue (maximal for the 1000-Hz test tone) to a type seen in long-term or high-level fatigue (maximal at frequencies higher than that of the inducer or fatiguing tone). A common cochlear origin and a continuity between the mechanisms of ipsilaterally induced adaptation and high-level fatigue are suggested by the data.

Loudness reduction and adaptation induced by a contralateral tone.

An intermittent tone in one ear may induce a large decline in the loudness of a continuous tone in the contralateral ear [Botte et al., J. Acoust. Soc. Am. 72, 727-739 (1982)]. To uncover the basis for this induced loudness adaptation, the method of successive magnitude estimations was used to measure the loudness of a test tone in one ear during and after a single presentation of a brief inducer tone in the contralateral ear. Duration and frequency of the inducer were varied. The frequency of the test tone was set at 500, 1000, or 3000 Hz. Both inducer and test tones were at 60 dB SPL. When the inducer lasted 5 s or more and was at the same frequency as the test tone, the loudness of the test tone was reduced by 80% to 100% while the inducer was on. As the inducer frequency moved away from the test tone, the loudness reduction declined gradually except for a more marked drop at the point where the frequency separation exceeded the critical bandwidth. Loudness remained depressed after the inducer went off. Additional measurements showed that the amount of loudness reduction corresponded closely to the measured movement of the inducer's sound image away from the center of the listener's head (decentralization).

Simple and induced loudness adaptation.

Simple loudness adaptation is the decrease in loudness that takes place when a continuous sound is presented alone for a period of time. Simple adaptation normally occurs only when a sound is soft to begin with, no more than 30 dB above threshold; except for some persons with a retrocochlear lesion, sounds above 30 dB SL do not diminish in loudness over time. However, adaptation can be induced in at least two ways: (1) A steady sound to one ear, presented together with an intermittent sound to the contralateral ear, decreases in loudness by 50-60% within 3 min. (2) An otherwise steady sound that is intermittently increased in level by at least 5 dB becomes softer during its weaker periods. When, for example, a 40-dB tone is increased every 20 s to 60 dB for 15 s, its loudness decreases by about 50% within 3 min. We report measurements of both simple and induced adaptation on 10 persons listening to a 1 000-Hz tone via earphones or from a loudspeaker. The results provide an overview of both types of adaptation. They also permitted a correlational analysis that reveals some of the similarities and differences between the two kinds of adaptation.

Loudness adaptation, when induced, is real.

In two recent articles, Hood and Wade (1982) and Weiler et al. (1981) have argued that the loudness of a steady tone does not appear to decline over time unless listeners are given a reference sound by which to judge loudness. The present experiments show, by the method of successive magnitude estimation, that listeners do not need a reference sound in order (1) to track accurately the decline in the loudness of a tone slowly decreasing from 60 to 40 dB SPL or (2) to track the loudness decline of a constant-intensity tone under special conditions that lead to adaptation. Since a reference sound is not needed by listeners to track a decline in loudness, and since Hood and Wade and Weiler et al. have found a decline with a reference but not without, it follows that adding a reference sound to a sustained sound must induce adaptation that otherwise does not occur. In support of that interpretation, the present measurements show that when subjects are told to ignore the same reference sound as used by Hood and Wade and by Weiler et al.--an increment every 30 s to a steady tone--loudness still declines. The bigger the increment (20 dB v. 5 dB) and the longer (5 s v. 1 s), the more loudness declines. Thus, loudness adaptation may be induced not only by a contralateral intermittent sound (Botte et al., 1982) but also by an ipsilateral intermittent sound. However, under normal listening conditions at levels above about 30 dB SL, loudness does not adapt.

Loudness adaptation induced by an intermittent tone.

The loudness of a continuous 1000-Hz tone at 60 dB SPL was measured in the presence of an intermittent tone in the contralateral ear. Over 70 observers participated in a series of eight experiments. The method of successive magnitude estimation showed that the intermittent tone causes the steady tone to diminish in loudness within 2 or 3 min by 40% to 60%. The amount of this induced loudness adaptation depends weakly upon the presentation rate, frequency, and level of the contralateral tone. Loudness reduction of the steady tone is coupled with loudness enhancement of the intermittent tone in the opposite ear. Induced loudness adaptation was also revealed by interaural and cross-modality matching. Induced loudness adaptation depends strongly on interaural interaction and is probably related to lateralization and interaural funneling of loudness. Adaptation induced by an intermittent tone stands in marked contrast to the near absence of loudness adaptation, except near threshold, when a continuous sound is presented alone.

[Auditory fatigue in individuals having sustained an acoustic trauma (author's transl)]. / La fatigue auditive chez les sujets ayant subi un traumatisme acoustique.

A comparison was made between losses of auditory sensitivity after a fatiguing sound exposure of the ear in two groups of subjects: audiometrically normal subjects and subjects with early acoustic trauma. Subjects with cochlear impairment sustained an auditory loss apparently less than that of normal subjects when this loss is measured at threshold level. However, at supraliminal levels the loss of sensitivity, as measured here, would seem to be equal in both groups of subjects. In fact, the dynamics of sonic variations, already reduced by the cochlear impairment, is even further decreased by the effects of fatigue.

[Auditory fatigue in man. Comparison of recovery at threshold and above threshold]. / Etude de la fatigue auditive chez l'homme. comparaison de la récupération au niveau du seuil et aux niveaux supraliminaires.

Using a 1 000-Hz pure tone, a TTS2 of 20 dB was produced in a group of subjects. Recovery from this TTS was studied at 1 500 Hz and the measurements were extended to 320 min to encompass the course of recovery, The recovery of the temporary impairment of threshold was plotted concurrently with that of the temporary masked threshold shift (TMTS) of the 1 500 Hz tone in the presence of a 700 Hz masking tone. This technique provided an indirect measurement of loudness loss at 10. 20, 30, 40, 50 and 60 dB SL. The time required for complete recovery depended upon whether one measured TTS or TMTS; the longest recovery times were, in respect of the masked threshold, at low sensation levels.

Temporary threshold shift, loudness, and auditory evoked potentials.

TTS2 of 20dB was produced in a group of subjects using a 1000 Hz pure tone. All TTS and related measurements were made at 1500 Hz. The recovery of TTS, and of TLS or 'temporary loudness shift' (measured against a reference tone at 20db, 40dB and 60dB SL in the opposite ear), as well as N1-P2 amplitude of the Vertex potential, were plotted. There was an orderly recovery of both TLS and TTS although the rate of recovery of the latter was noticeably more rapid. Recovery of N1-P2 amplitude was much less orderly, although it did recover in much the same way. When the amplitudes were measured at 40dB SL the recovery was more orderly and followed the course of TTS more closely. It was concluded that any relation between N1-P2 amplitude and growth of loudness was indirect.

[Auditory-evoked responses to a monaural or a binaural click, recorded from the vertex, as in two temporal derivations; effect of interaural time differences (author's transl)]. / Réponses évozuées auditives à un clic monaural et à un clic binaural enregistrèes au vertex et dans deux d

The auditory-evoked responses have been recorded on 5 subject by vertex, right temporal and left temporal electrodes simultaneously. 30 dB sensation level clicks were used as stimuli; one click was presented only to the right ear, or one click only to the left ear, or one click to the right ear and another click to the left ear with a variable interaural time difference in this latter case (0-150 ms). The N-P amplitude variations and the N and P latency variations have been studied and compared to those observed in the perceived lateralizations of the sound source.

Temporary threshold shift and the auditory evoked response. A preliminary report.

A preliminary study was performed on 5 normal subjects to investigate and compare the reduction and recovery of the auditory evoked response (AER), and to compare this with the temporary threshold shift (TTS) that occurs with fatiguing sounds. The findings are discussed in relation to the basic nature of the AER.