Search PubMed⌕ Search

Biomedical subjects

H T Jansen

Publications and source records attributed to H T Jansen.

17 recordsLinked to original sources
PubMed1997

Identification and distribution of neuroendocrine gonadotropin-releasing hormone neurons in the ewe.

The final common pathway controlling reproductive function in vertebrates is the GnRH neuron and its projection to the median eminence (ME), site of peptide release into the pituitary portal system. GnRH neurons are widely distributed; therefore we sought to test the hypothesis that those projecting to the ME are located in specific regions. We used as a model the sheep, a species in which a great deal of information regarding the physiology of GnRH secretion is known. To identify cells projecting to the ME (i.e., neuroendocrine neurons), ewes (n = 10) received injections into the ME of neuronal tract-tracing compounds: cholera toxin-beta subunit (CT-beta) or one of two fluorescent compounds (rhodamine isothiocyanate or fluorescein-conjugated dextran). Forty-eight h later, animals were perfused intracranially and their brains were processed for immunocytochemical localization of GnRH and CT-beta using a dual-immunofluorescent procedure or by single-label immunofluorescent visualization of GnRH combined with direct visualization of fluorescent tracers. Small, well-circumscribed injections into the ME were made successfully in 6 of 10 animals, and these overlapped the location of GnRH terminals and fibers. Neuroendocrine GnRH neurons (those GnRH neurons containing retrogradely transported tracer) were identified throughout their previously reported range: within the diagonal band of the Broca/medial septal region, medial preoptic area (MPOA), anterior hypothalamic area, and medial basal hypothalamus. Although the absolute number of neuroendocrine GnRH neurons varied by region, the percentage of the total GnRH population within each of these areas that was retrogradely labeled did not differ (p > 0.05). Injections placed unilaterally within the ME labeled a similar proportion of GnRH cells both ipsilateral and contralateral to the injection site in all areas except the MPOA, where ipsilaterally labeled cells were approximately twice as numerous as those labeled contralaterally. Injections that missed the ME and were placed either into the third ventricle or into the arcuate nucleus labeled only 0.5% and 4-11% of GnRH neurons, respectively. These results do not support the hypothesis that in the ewe, GnRH neurons projecting to the ME are localized to specific regions. Thus, we postulate that GnRH release into the hypophyseal portal system reflects the output of GnRH neurons located in multiple areas.

Animals↗
PubMed1996

A subset of estrogen receptor-containing neurons project to the median eminence in the ewe.

The neural pathways responsible for conveying the steroid feedback signals that ultimately affect reproductive neuroendocrine function remain largely undefined. One possibility involves a direct projection from estrogen receptor (ER)-containing neurons to the median eminence (ME), a site of neuroendocrine peptide release. To examine this possibility, 8 ewes received stereotaxic injections of the retrograde neuronal tract-tracing compound cholera toxin-beta subunit (CT beta) into the ME. Neurons sending projections to the ME and containing ER were identified using a dual-label immunoperoxidase method. Double-labeled cells were found in distinct regions: (1) the ER-rich arcuate nucleus (ARC) that contained the greatest number of double-labeled cells, and (2) the organum vasculosum of the lamina terminalis (OVLT) which contained a very consistent, but low, number of double-labeled cells. While a fairly large number of retrogradely-labeled ARC neurons containing ER were identified, the majority of ER-containing ARC neurons were unlabeled and thus send projections elsewhere. Other regions containing high concentrations of ER-positive cells such as the medial preoptic area (MPOA), anterior hypothalamic area, and ventrolateral portion of the ventromedial hypothalamic nucleus, were devoid of double-labeled cells. Similarly, regions rich in neuroendocrine neurons such as the periventricular hypothalamus and paraventricular and supraoptic hypothalamic nuclei contained no double-labeled cells. These results suggest that modulation of neuroendocrine secretory activity may occur directly at the level of the ME by ER-containing neurons located within restricted regions of the hypothalamus and forebrain. However, the relatively low proportion of ER-containing neurons projecting to the ME suggests that the influence of estradiol upon neuroendocrine function also may include target sites other than the ME.

Animals↗
PubMed1996

Dopaminergic A14/A15 neurons are activated during estradiol negative feedback in anestrous, but not breeding season, ewes.

A major factor responsible for seasonal anestrus in sheep is a striking increase in the ability of estradiol (E) to inhibit pulsatile GnRH and LH secretion. Previous studies suggest that dopaminergic neurons in the A14 and A15 groups of the ovine hypothalamus play a key role in conveying the inhibitory effects of E in anestrous ewes. The present study tested the hypothesis that A14/A15 neurons in anestrous ewes are activated in response to E, and that this activation is specifically related to seasonal changes in E negative feedback. Expression of the immediate early gene products, Fos and the Fos-related antigens (FRAs), was used as a marker of neuronal activation. Ovariectomized anestrous ewes received either blank implants (no E) or 0.5-cm long E implants sc and were killed 6 h later (E+6h) or 7 days later (E+7d and no E groups). During the breeding season, two additional groups of ovariectomized ewes were perfused 7 days after insertion of either blank or E implants. During anestrus, E completely suppressed LH pulses in the E+7d group, but had no effect in the E+6h group. In the E+7d anestrous group, there was also a significant increase in the mean percentage of tyrosine hydroxylase (TH)-positive cells that expressed nuclear Fos/FRAs in A14 and A15 areas compared to that in either the no E or E+6h group. By contrast, during the breeding season, E had no effect on LH pulse frequency, and there were relatively few TH-positive cells in A14 and A15 that coexpressed Fos/FRAs in either the no E or E+7d group. No significant steroidal or seasonal differences in Fos/FRA expression were seen in other hypothalamic dopaminergic cell groups (A12 and A13) or in the preoptic area-anterior hypothalamus or suprachiasmatic nucleus. Furthermore, E did not alter the total number of TH-positive neurons in A14/A15 or other cell groups. There were seasonal differences in the number of TH-positive neurons, with a significantly greater number of cells in the A13 and A15 of breeding season animals compared to anestrous ewes. Thus, E increased Fos/FRA expression in A14/A15 neurons only during anestrus at a time when it also inhibited LH pulse frequency. These findings are consistent with the view that activation of dopaminergic cells in A14 and A15 is a critical link in the chain of events leading to seasonal shifts in sensitivity to E negative feedback in the ewe.

Anestrus↗
PubMed1995

Disruption of reproductive rhythms and patterns of melatonin and prolactin secretion following bilateral lesions of the suprachiasmatic nuclei in the ewe.

To determine whether the photoperiodic responses of reproductive and prolactin (PRL) rhythms in the ewe requires an intact suprachiasmatic nucleus (SCN) driving the pineal rhythm of melatonin secretion, four groups of ovary-intact ewes over a 6-year period were subjected to bilateral (n = 40) or sham lesions (n = 15) of the SCN. Animals were exposed to an alternating 90-120 day photoregimen of 9L:15D and 16L:8D photoperiods. Blood samples taken twice weekly were assayed for prolactin and for progesterone to monitor oestrous cycles. On several occasions blood samples also were taken at hourly intervals for 24 h and analyzed for melatonin. Melatonin concentrations in sham lesioned ewes were basal during the lights-on period and rose robustly during darkness. Those sheep bearing unilateral lesions of the SCN (n = 13) or where the lesion spared the SCN entirely (n = 8) had patterns of melatonin secretion similar to sham ewes. The remaining ewes, having complete (n = 9) or incomplete bilateral (n = 8) destruction of the SCN, with one exception, had disrupted patterns of melatonin secretion. The nature of this disruption varied from complete suppression to continuously elevated levels. In lesioned ewes where melatonin secretion was not affected the onset and cessation of ovarian cycles were similar to sham ewes; stimulation of oestrous cycles under 9L:15D and cessation of oestrous cycles under 16L:8D. In contrast, 13 of 17 ewes with disrupted melatonin secretion also exhibited disrupted patterns of ovarian activity. In these animals oestrous cycles were no longer entrained by photoperiod but still occurred in distinct clusters, that is, groups of cycles began and ended spontaneously. Sheep with normal melatonin patterns showed low levels of PRL secretion during short days and elevated PRL levels during long days. However, 8 of 13 ewes with disrupted melatonin showed patterns of PRL secretion that were no longer entrained by photoperiod. A minority of ewes with disrupted melatonin patterns still showed reproductive (n = 4) and PRL (n = 5) responses similar to those of sham-lesioned ewes. These results show that bilateral destruction of the SCN in the ewe disrupts the circadian pattern of melatonin secretion and that this disruption usually, but not always, is associated with altered photoperiodic responses. These results strongly suggest that the SCN are important neural elements within the photoperiod time-keeping system in this species. A role for the SCN in the generation of endogenous transitions in reproductive activity (refractoriness) and prolactin secretion is not supported.

Animals↗
PubMed1994

Single- and double-label immunocytochemical study of the ovine suprachiasmatic nucleus (SCN): GABAergic and peptidergic relationships.

This study evaluated the neuropeptide and neurotransmitter content of the ovine suprachiasmatic nucleus (SCN) using both single- and double-label immunocytochemical methods. Single-label immunocytochemistry identified a few lightly labeled gamma aminobutyric acid (GABA) cells within the SCN as well as a dense plexus of fibers staining positive for the GABA biosynthetic enzyme, glutamic acid decarboxylase (GAD). Vasoactive intestinal polypeptide (VIP) fibers exhibited a similar distribution to GAD fibers; VIP cells were found throughout the SCN, as well as in the paraventricular (PVN) and supraoptic nuclei. Both GAD and VIP fibers exited dorsally from the SCN towards the PVN. Neurophysin (NP) and neuropeptide-Y (NPY) fibers were sparsely distributed throughout the SCN. Double-label immunocytochemistry revealed that GAD varicosities were often in close apposition to VIP cells. These results confirm the presence of GABAergic elements within the sheep SCN. Furthermore, they raise the possibility of a GABAergic modulation of VIP neuronal activity within the ovine SCN.

Animals↗
PubMed1993

A re-evaluation of the effects of gonadal steroids on neuronal activity in the male rat.

Single unit activity (SUA) was recorded from 77 cells located in the arcuate nucleus (ARC) and medial preoptic area (MPA) of anesthetized, intact male rats. Animals were administered vehicle, testosterone (T; 5 or 50 micrograms) or 17 beta-estradiol (E; 0.5 microgram) intravenously and SUA was monitored for 8-12 min. T (50 micrograms) reduced SUA in 50% of ARC units and 44% of MPA units within 2.1 +/- 0.46 and 3.3 +/- 0.92 min, respectively. Inhibition of ARC SUA was more pronounced than MPA SUA. A small percentage (9%) of ARC units were excited by T. E reduced SUA in 29% of ARC units and 27% of MPA units. Single doses of 5 micrograms T did not affect ARC activity. However, when followed within 10 min by an additional dose of 5 or 50 micrograms T, 30% and 43% of ARC units were inhibited, respectively. Doses (10 micrograms) of T produced plasma T concentrations within physiological limits, although 50 micrograms doses produced supraphysiological T levels. Neither dose affected circulating LH concentrations. We conclude that physiological and supraphysiological concentrations of T can rapidly affect SUA within the ARC.

Analysis of Variance↗
PubMed1993

Circannual rhythms in the ewe: patterns of ovarian cycles and prolactin secretion under two different constant photoperiods.

The purpose of this experiment was to determine whether circannual rhythms of reproductive activity and prolactin secretion are expressed differently in ewes housed under two different constant photoperiods and restricted temperatures. Eleven ovary-intact ewes housed previously under constant 12L:12D were used. One group (n = 6) was switched to 8L:16D while the other group (n = 5) remained on 12L:12D. Ovarian cycles and prolactin concentrations were monitored for more than 3 yr. The switch from 12L:12D to 8L:16D caused a change from cycles of varied length to regular 17-day cycles within 25 +/- 3 days in all 6 ewes. Subsequently, one complete circannual cycle (300.8 +/- 10.2 days) of breeding and nonbreeding activity was expressed in all ewes, but it was repeated in only 2 ewes. Ewes maintained on 12L:12D cycled at irregular intervals, and only 2 exhibited a distinct circannual rhythm of anestrus and breeding cycles. Episodic variations in ovarian cycle density were observed in most ewes in both groups. The period of this rhythm was similar between groups (290 +/- 19 and 278 +/- 16 days) and differed from 365 days (p < 0.05). Plasma prolactin exhibited a circannual rhythm under both 8L:16D and 12L:12D with a periodicity different from 365 days. We conclude that photoperiod length does not influence the expression of circannual reproductive and prolactin rhythms in the ewe. The absence of a circannual rhythm of breeding and nonbreeding activity, in the presence of circannual changes in ovarian cycle density, suggests that expression of an underlying endogenous oscillator controlling LH secretion was masked or damped.

Anestrus↗
PubMed1993

Olfactory bulb removal does not prevent gonadotropin or prolactin responses to changing photoperiod in the ewe.

The purpose of this study was to determine if bilateral olfactory bulb removal (Bulbx) alters photoperiod-induced changes of gonadotropin and prolactin secretion in the ewe. Ovariectomized (group 1; n = 12) or ovariectomized estradiol-treated (group 2; n = 12) Suffolk ewes underwent Bulbx (7 per group) or sham operations (5 per group). All ewes subsequently were placed into photochambers and exposed to a photoregimen of alternating 16 h light/8 h dark and 10 h light/14 h dark photoperiods. Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were determined in blood samples taken twice weekly from group 2 ewes. At the end of each 90-day photoregimen blood samples from all ewes in both groups were taken at frequent intervals for 4 h to determine LH pulse parameters. During the initial 16 h light/8 h dark photoperiod, plasma melatonin concentrations were determined for group 2 ewes during a 24-hour period. The completeness of Bulbx was determined at time of necropsy for all Bulbx ewes. In addition, the functional completeness of Bulbx was determined in group 2 ewes by exposing them to ram's wool and measuring changes in LH secretion. Bulbx did not affect either basal or photoperiod-induced changes in LH, FSH and prolactin in group 2 ewes. LH pulse parameters varied with photoperiod but were not significantly (p > 0.05) affected by Bulbx in either group 1 or group 2 ewes. The normal nocturnal elevation in plasma melatonin concentrations was unaffected by Bulbx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

N-methyl-D, L-aspartate induces a transient increase in LH secretion in the seasonally anestrous ewe.

The primary objective of this study was to determine the LH response to an excitatory amino acid agonist, N-methyl-D, L-aspartate (NMA) in the seasonally anestrous ewe. In experiment 1, 3 i.v. injections of NMA were given; doses of 0.5, 1.5 and 4.5 mg/kg BW were tested. LH response to NMA depended on the dose. There was little response to the lowest dose. All animals responded to the first injection of the intermediate and the highest doses (mean pulse amplitude: 9.2 +/- 0.4 and 6.8 +/- 1.2 ng ml, respectively). The responses to the second or third injections of both doses were variable and were either absent or reduced compared to that of the first. In experiments 2 and 3, ewes were given 3 injections of normal saline (NS) followed by 3 injections of NMA (1.25 and 4.5 mg/kg BW, respectively) at 2 hr intervals. The last injection of NMA was followed 2 hr later by an injection of GnRH (3.0 ng/kg BW). In experiment 2, the first NMA injection induced an immediate LH pulse (mean pulse amplitude: 8.0 +/- 1.6 ng/ml) in all ewes, however, the second and third injections induced LH pulses in only 25% and 75% (mean pulse amplitude: 2.2 and 2.4 +/- 0.6 ng/ml) of the ewes, respectively. In experiment 3, NMA increased mean LH release (P less than 0.05) after all injections, but responsiveness to the third injection was reduced in some ewes. GnRH injections induced LH release in all ewes in experiments 2 and 3 (mean pulse amplitude: 6.9 +/- 1.8 and 6.4 +/- 2.2 ng/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1991

Persistence of a circannual rhythm of plasma prolactin concentrations in ewes exposed to a constant equatorial photoperiod.

Circulating concentrations of prolactin were monitored for 3 yr in intact ewes kept either outdoors or indoors in a fixed equatorial photoperiod (12L:12D) and restricted range of environmental temperatures. Prolactin data were analyzed by spectral analysis. In all ewes kept outdoors, concentrations of prolactin showed robust circannual rhythms with a single predominant period of 359 days. In ewes kept indoors, the range of significant periods varied from 35 to 532 days. Although all ewes kept indoors showed a significant rhythm with a period of 354 days, this clearly was not the predominant period in all. The amplitude of the rhythm in ewes kept indoors was significantly lower (p less than 0.01) than that of ewes kept outdoors. Although the annual rhythm of circulating prolactin typical of ewes kept outdoors was significantly compromised in animals kept under a constant 12L:12D photoperiod and restricted environmental temperature range, there was evidence of an endogenous circannual rhythm.

Animals↗
PubMed1989

Comparing the cardiac vagolytic effects of atropine and methylatropine in rhesus macaques.

Atropine and methylatropine (190 nmol/kg) were compared in rhesus monkeys (Macaca mulatta) for their ability to produce a cardiac vagal blockade using a noninvasive estimate of respiratory sinus arrhythmia (RSA). Twelve monkeys received both drugs via intravenous (IV) and intramuscular (IM) routes of administration and were monitored for 3 hr after treatment. Both drugs, regardless of the route of administration, reduced RSA amplitude. At this dose, methylatropine was more effective than atropine in its ability to reduce RSA amplitude, heart period (HP; beat-to-beat interval), and overall heart period variability (HPV). Estimated RSA amplitude and HPV returned to basal levels significantly earlier after IM atropine administration than after IV treatment. Methylatropine did not exhibit any route effects. In addition, the mean decrease in RSA amplitude and HPV for the IM route of atropine sulfate was significantly less than that for the IV route. Serum atropine concentrations correlated significantly with all variables after IM treatment but only with RSA and HPV after IV treatment. Methylatropine may therefore be more useful than atropine as a pharmacologic challenge drug for detecting organophosphorus (OP) exposure because of its longer duration of action, lack of route of administration differences, and less likelihood of crossing the blood-brain barrier. Further studies are needed to fully evaluate methylatropine's potential in the challenge method of OP detection.

Animals↗
PubMed1989

Time of the sidereal year affects responsiveness to the phase-resetting effects of photoperiod in the ewe.

Two groups of ovary-intact ewes were placed in separate photochambers on the day of the vernal equinox (VE). One group was exposed to a 16 h light:8 h dark (16L:8D) photoperiod and the other to 8L:16D. On the day of the summer solstice (SS) and at 90-91-day intervals thereafter [autumnal equinox (AE), winter solstice (WS), VE and SS], each group was changed to the opposite photoperiod. The latent period between each change and either onset or cessation of cycles, as determined by measuring blood progesterone concentrations, was recorded. The latent period between change to 8L:16D and onset of cycles was shortest after the exposure at AE and longest after exposure at WS (P less than 0.001). The latent period after AE was shorter (P less than 0.001) than after VE. The correlations were small between ambient temperature and interval to onset of cycles. The latent period to cessation of cycles in response to 16L:8D was shorter after SS exposure than after WS exposure (P less than 0.01), but other differences were not significant. There was a strong (r = -0.94, P less than 0.05) negative correlation between interval to cessation of cycles and ambient temperature. Cessation of cycles in response to 16L:8D occurred more rapidly (P less than 0.001) than onset in response to 8L:16D. These results show that responsiveness to the inductive effects of photoperiod varies significantly with time of the sidereal year.

Animals↗
PubMed1988

Vagal tone monitoring: a potential indicator of anti-cholinesterase exposure in Macaca mulatta.

A vagal tone monitor (VTM) was used to evaluate cardiac rhythm changes in Rhesus monkeys (Macaca mulatta) after intramuscular (i.m.) administration of an anti-cholinergic (atropine sulfate), two carbamates (pyridostigmine bromide and physostigmine salicylate), and combinations of pyridostigmine and atropine. Twelve monkeys were studied in 4 experiments using Latin Square blind designs. Experiment I tested the VTM responses to atropine sulfate injections of 0, 14, 44 and 140 micrograms/kg. Experiment II tested the responses to 0, 100, 200 and 400 micrograms/kg pyridostigmine injections. Experiment III tested the responses to physostigmine injections of 0, 25, 50 and 100 micrograms/kg. Experiment IV tested the same atropine sulfate treatments as Experiment I 30 min after a pyridostigmine pretreatment of 200 micrograms/kg. The VTM analysis produced an estimate of vagal tone (V) every 30 s, and V was averaged over 15 min. The results indicated that V responded more to physostigmine and atropine than pyridostigmine. There was also an attenuated response to atropine following pyridostigmine pretreatment. The attenuated response had been demonstrated earlier in organophosphate (OP) treated dogs. The results suggest that V may be used as a non-invasive indicator of cholinergic drug effects.

Acetylcholinesterase↗
PubMed1987

In vivo interactions of aluminum with hepatic cytochrome P-450 and metallothionein.

Male Sprague-Dawley rats (three per treatment group) were administered 0, 2, 10, 20, or 40 mg aluminum per kilogram ip per day for 3 days as aluminum chloride in saline. Animals were killed 24 hr later. Aluminum was found to inhibit hepatic drug metabolism in a dose-dependent fashion. The lowest dose (2 mg or 75 mumol/kg) had no effect on the parameters measured, whereas the highest dose (40 mg or 1.5 mmol/kg) caused a 52% decrease in cytochrome P-450, a 71% decrease in p-nitrophenetole O-deethylase activity, and a 77% decrease in ethylmorphine N-demethylase activity. Hepatic glutathione levels were unaffected by aluminum, whereas metallothionein (MT) was induced in both liver and kidney. The distribution of endogenous metals normally associated with MT was altered by aluminum administration. At the highest dose of aluminum (40 mg/kg), zinc levels were increased in liver cytosol (154%), while copper levels were unchanged in liver, but decreased in kidney (70%). Aluminum was present in the liver and kidney. Of the aluminum in the liver, less than 5% was in the cytosol, bound to a MT-like protein. It is concluded that acute ip administration of aluminum adversely effects hepatic drug metabolism and that aluminum induces and binds to MT or a MT-like protein.

Aluminum↗
PubMedDate not supplied

Estrogenic and antiestrogenic actions of PCBs in the female rat: in vitro and in vivo studies.

A series of studies were performed to examine the effects of various PCB congeners [3,4,3',4'-TCB (PCB77), 2,5,2',5'-TCB (PCB52), 4' OH-2,4,6-TCB (OHPCB)] and a complex PCB mixture (Aroclor 1242; A1242) on the weights and patterns of cell proliferation of immature rat uteri in vivo and the effects of A1242 on gonadotropin release by dispersed anterior pituitary cells in vitro. Immature (20-day) rats were treated ip with corn oil (vehicle), PCBs, or 17 beta-estradiol (E2) once or daily for two consecutive days. Except for PCB77, all PCBs and E2 produced significant increases in uterine weights (P < 0.01) and increases in uterine 3H-thymidine labeling. PCB77 attenuated (P < 0.01) the increase in uterine weight due to either A1242 or E2 treatment. Cultured anterior pituitary cells exposed to varying concentrations of A1242 (0.1 to 50 ppm) exhibited enhanced gonadotropin responses to gonadotropin-releasing hormone (GnRH) similar to that of E2. These results demonstrate that PCBs can produce either estrogenic or antiestrogenic effects.

Animals↗
PubMedDate not supplied

Effects of atropine on respiratory sinus arrhythmia (RSA) in the rhesus macaque.

Twelve juvenile to adult rhesus macaques were administered atropine sulfate (0, 14, 44, and 140 mcg/kg IM). The amplitude of the respiratory sinus arrhythmia (RSA) in the rhesus macaque was estimated using a Vagal Tone Monitor (VTM). The estimate of RSA (termed V; vagal tone) was significantly reduced for nearly 3 hr after all doses of atropine, suggesting possible central nervous system effects. Heart period (R-R interval) was reduced briefly after dosing. Overall heart period variability (HPV) was depressed after all doses of atropine. The amount of atropine required to decrease HPV and V by 30% was similar to that reported for the human. The rhesus monkey was determined to have little resting vagal tone as estimated by V. A large slow wave oscillation contributed to the overall variability in heart period. It is concluded that the rhesus monkey exhibits a similar sensitivity to atropine as did the human and, therefore, provides a useful model for the study of cholinergic drug actions and their effects on RSA.

Animals↗