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D B Parfitt

Publications and source records attributed to D B Parfitt.

11 recordsLinked to original sources
PubMed2005

Relation between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-adrenal (HPA) axis during repeated stress.

Previous work has indicated that acute and repeated stress can alter thyroid hormone secretion. Corticosterone, the end product of hypothalamic-pituitary-adrenal (HPA) axis activation and strongly regulated by stress, has been suggested to play a role in hypothalamic-pituitary-thyroid (HPT) axis regulation. In the current study, we sought to further characterize HPT axis activity after repeated exposure to inescapable foot-shock stress (FS), and to examine changes in proposed regulators of the HPT axis, including plasma corticosterone and hypothalamic arcuate nucleus agouti-related protein (AGRP) mRNA levels. Adult male Sprague-Dawley rats were subjected to one daily session of inescapable FS for 14 days. Plasma corticosterone levels were determined during and after the stress on days 1 and 14. Animals were killed on day 15, and trunk blood and brains were collected for measurement of hormone and mRNA levels. Repeated exposure to FS led to a significant decrease in serum levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4). Stress-induced plasma corticosterone levels were not altered by repeated exposure to the stress. Despite the decrease in peripheral hormone levels, thyrotropin-releasing hormone (TRH) mRNA levels within the paraventricular nucleus of the hypothalamus were not altered by the stress paradigm. Arcuate nucleus AGRP mRNA levels were significantly increased in the animals exposed to repeated FS. Additionally, we noted significant correlations between stress-induced plasma corticosterone levels and components of the HPT axis, including TRH mRNA levels and free T4 levels. Additionally, there was a significant correlation between AGRP mRNA levels and total T3 levels. Changes in body weight were also correlated with peripheral corticosterone and TRH mRNA levels. These results suggest that repeated exposure to mild-electric foot-shock causes a decrease in peripheral thyroid hormone levels, and that components of the HPA axis and hypothalamic AGRP may be involved in stress regulation of the HPT.

Adaptation, Physiological↗
PubMed2004

Antidepressants blunt the effects of inescapable stress on male mating behaviour and decrease corticotropin-releasing hormone mRNA expression in the hypothalamic paraventricular nucleus of the Syrian hamster (Mesocricetus auratus).

Stress decreases sexual activity. However, emerging research suggests that the psychological aspect of control prevents the detrimental effects of stress on male mating behaviour. The present study examined the effects of chronic escapable/inescapable stress on mating behaviour in the male Syrian hamster. Additionally, the ability of the antidepressant clomipramine to prevent the adverse effects of stress on mating behaviour was explored. In this paradigm, two groups received the same electric footshock stress, but differed in the psychological aspect of control. Cohorts were divided into two groups. One group received clomipramine via a sugar water solution while the other received plain sugar water. Mating behaviour was quantified before and after 12 consecutive days of stress. The morning following the final stress and behaviour session, trunk blood and brains were collected to assess: (i) plasma concentrations of testosterone and glucocorticoids and (ii) corticotropin-releasing hormone (CRH) mRNA expression within the paraventricular nucleus of the hypothalamus (PVN). In the drug-free groups, several aspects of mating behaviour were disrupted by inescapable but not escapable stress, including anogenital investigation before the first ejaculation and time of first ejaculation. Additionally, both escapable and inescapable stress caused a decrease in total hit rate compared to the no-stress control group. Unlike the sugar-water treated animals, hamsters in either stress condition receiving clomipramine showed no differences in anogenital investigation, time of first ejaculation, hit rate, or any other aspect of mating behaviour measured, compared to the clomipramine no-stress control males. The stress-induced inhibition of mating behaviour could not be explained by changes in baseline plasma concentrations of testosterone or total glucocorticoids; these values did not vary between any of the six treatment groups. It was found that clomipramine lowers CRH mRNA expression in the PVN by 74%, regardless of stressor conditions. The results of the present study have broad implications for understanding the relationships between stress, depression and reproduction, and for the treatment of people and animals suffering from the adverse effects of stress.

Animals↗
PubMed2001

Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea.

Cross-sectional studies of exercise-induced reproductive dysfunction have documented a high proportion of menstrual cycle disturbances in women involved in strenuous exercise training. However, longitudinal studies have been needed to examine individual susceptibility to exercise-induced reproductive dysfunction and to elucidate the progression of changes in reproductive function that occur with strenuous exercise training. Using the female cynomolgus monkey (Macaca fascicularis), we documented changes in menstrual cyclicity and patterns of LH, FSH, estradiol, and progesterone secretion as the animals developed exercise-induced amenorrhea. As monkeys gradually increased running to 12.3 +/- 0.9 km/day, body weight did not change significantly although food intake remained constant. The time spent training until amenorrhea developed varied widely among animals (7-24 months; mean = 14.3 +/- 2.2 months) and was not correlated with initial body weight, training distance, or food intake. Consistent changes in function of the reproductive axis occurred abruptly, one to two menstrual cycles before the development of amenorrhea. These included significant declines in plasma reproductive hormone concentrations, an increase in follicular phase length, and a decrease in luteal phase progesterone secretion. These data document a high level of interindividual variability in the development of exercise-induced reproductive dysfunction, delineate the progression of changes in reproductive hormone secretion that occur with exercise training, and illustrate an abrupt transition from normal cyclicity to an amenorrheic state in exercising individuals, that is not necessarily associated with weight loss.

Amenorrhea↗
PubMed2001

Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training.

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

Amenorrhea↗
PubMed1999

GnRH mRNA increases with puberty in the male Syrian hamster brain.

Puberty in the male Syrian hamster (Mesocricetus auratus) is characterized by decreased responsiveness to testosterone mediated negative feedback, but the neural mechanism for this change remains elusive. We hypothesized that decreased inhibition of the gonadotropin-releasing hormone (GnRH) system results in increased neurosecretory activity, which includes an increase in GnRH gene expression. This study examined GnRH mRNA in male hamsters before and after puberty, and sought to determine if any increase in mRNA was specific to particular subpopulations of GnRH neurones. Brains were collected from 21-day-old prepubertal males (n = 5) and 56-day-old postpubertal males (n = 5). Alternate 10 microm coronal sections from fresh-frozen brains were collected throughout the septo-hypothalamic region, and 25% of those sections were processed for in-situ hybridization histochemistry using an 35S-riboprobe complementary to hamster GnRH. No differences were observed in the number of GnRH mRNA expressing cells in any region, but in the diagonal band of Broca (DBB)/organum vasculosum of the lamina terminalis (OVLT) there was a significant increase in labelling intensity (defined as area of the cell occupied by silver grains) in postpubertal males. A second analysis compared the frequency distributions of cells based on labelling intensity between prepubertal and postpubertal males. This analysis revealed significant differences between the two frequency distributions in all areas analysed (DBB/OVLT, medial septum (MS), and preoptic area (POA)). Furthermore, examining the distribution of cells in these regions revealed a shift to the right in the postpubertal population of cells, which indicated an increased number of GnRH neurones with greater labelling intensity. These data clearly demonstrate increased GnRH mRNA during puberty. Furthermore, they suggest that the previous observation of brain region specific pubertal decreases in GnRH-immunoreactivity only within the DBB/OVLT and MS but not the POA are not due to differential levels of GnRH gene expression, but could indicate increased release from these neurones during puberty.

Aging↗
PubMed1998

Fos-immunoreactivity within the extended amygdala is correlated with the onset of sexual satiety.

We hypothesized that c-fos expression in the medial amygdala (Me), the bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA) of the male Syrian hamster brain correlated with sexual satiety. To address this hypothesis, males were mated for 4 consecutive days. Experiment 1 determined whether the number of Fos-immunoreactive (Fos-ir) nuclei was equivalent in two groups of males mated to sexual satiety, one group of rested males (9.67 +/- 0.80 ejaculations) and a second group mated for 4 consecutive days (3.50 +/- 0.56 ejaculations). Fos-ir was increased within the caudal posterodorsal Me (cMePD), the anterodorsal and posteroventral subdivisions of the posteromedial BNST [BNSTpm(ad) and BNSTpm(pv)], the dorsolateral MPOA, and the medial preoptic nucleus of all males mated to sexual satiety compared to nonmated controls. In addition, Fos-ir "clusters" within the cMePD and BNSTpm(ad) were present in males mated to satiety regardless of the number of ejaculations. However, all males achieved multiple ejaculations. Therefore, Experiment 2 examined whether two groups of males stopped at one ejaculation exhibit different patterns of Fos-ir depending on proximity to sexual satiety. Brains of consecutively mated males, closer to satiety than rested males, showed greater BNSTpm(pv) Fos-ir and 5/6 males, but no rested male, exhibited cMePD Fos-ir clusters. These results support the hypothesis that cMePD and BNSTpm(pv) neuronal activation is associated with satiety and may constitute a discrete circuit to terminate mating.

Amygdala↗
PubMed1998

Pheromones elicit equivalent levels of Fos-immunoreactivity in prepubertal and adult male Syrian hamsters.

Male reproductive behavior in the Syrian hamster is dependent on both pheromones from the female and the presence of gonadal steroid hormones. The pheromones are contained within female hamster vaginal secretions (FHVS) and stimulate anogenital investigation and mounting by the male. Administration of testosterone to castrated male hamsters facilitates anogenital investigation, mounts, and intromissions in adults, but elicits only anogenital investigation in prepubertal males. One hypothesis for why the full complement of reproductive behaviors is not activated by testosterone in prepubertal males is that the neural processing of pheromonal cues encountered during anogenital investigation is different in juveniles and adults. In the present experiment, we investigated the influence of sexual maturity on Fos expression in response to FHVS in the male Syrian hamster. We predicted a greater increase in Fos-immunoreactivity after exposure to FHVS within the neural circuit mediating male reproductive behaviors in adult compared to prepubertal males. Intact adult and prepubertal males were exposed to either a clean cotton swab or a swab containing FHVS. We found that, compared to animals exposed to a clean cotton swab, both prepubertal and adult males exposed to FHVS have a greater amount of Fos-immunoreactivity within several brain nuclei comprising the neural circuit mediating male reproductive behavior. Furthermore, this Fos response was equivalent in the two age groups. These results suggest that the inability of the prepubertal male hamster to perform the full repertoire of male reproductive behaviors is not due to a lack of a neuronal activation in response to the pheromonal cues present in FHVS.

Age Factors↗
PubMed1995

Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe.

This study was designed to test the hypothesis that endogenous opioid peptides (EOP) mediate the negative feedback action of estradiol on GnRH pulse size in breeding season ewes. If this hypothesis is correct, one would predict that an EOP antagonist should increase GnRH pulse size in estradiol-treated ovariectomized (OVX+E), but not in OVX, ewes. We, therefore, examined the effects of naloxone on GnRH pulse profiles in the hypophyseal portal blood of OVX and OVX+E ewes (n = 6/group). Samples were collected every 10 min for 6 h before, 6 h during, and 4 h after naloxone infusion. Estradiol treatment decreased GnRH pulse size and increased GnRH pulse frequency. Naloxone treatment had no effect on GnRH pulse frequency, but significantly increased GnRH pulse size. However, this stimulatory action of naloxone on GnRH pulse size was evident in both OVX and OVX+E ewes. These results are thus not consistent with the hypothesis that EOP mediate the negative feedback action of estradiol. Interestingly, naloxone not only increased GnRH pulse amplitude, but also prolonged the duration of GnRH release during a pulse. To obtain a more precise characterization of the effects of naloxone on the dynamics of GnRH release, pulse profiles in six OVX ewes were examined in hypophyseal portal blood sampled every minute for 4 h before and 4 h during naloxone infusion. Naloxone again increased both the amplitude and duration of GnRH pulses. The increase in GnRH pulse duration was caused by a prolongation of both the plateau and declining phases of the GnRH pulse. In addition to these effects on GnRH release during a pulse, naloxone increased the amount of GnRH collected between pulses in both experiments. The stimulatory effects of naloxone on GnRH release in OVX ewes indicate that the role of EOP in the control of GnRH is not limited to mediating the feedback actions of steroids. In particular, the dramatic effects of naloxone on GnRH pulse shape and interpulse GnRH levels raise the possibility that EOP play an important role in synchronizing the activity of the GnRH neurons involved in episodic GnRH secretion.

Animals↗
PubMed1993

Suppression of luteinizing hormone secretion during short-term fasting in male rhesus monkeys: the role of metabolic versus stress signals.

One day of fasting leads to a significant suppression of pulsatile LH secretion in adult male rhesus monkeys that is evident within the first 4-6 h after a missed meal. Restricting food intake may suppress the central drive to the reproductive axis via metabolic signals occurring during the transition from a fed, energy storing state to a fasted, energy mobilizing state or via signals associated with the "psychological stress" imposed by withholding food. To distinguish between these two general types of signals, we chose the experimental strategy of providing monkeys with a great excess of calories on the day before fasting (i.e. overfeeding on the day before fasting) in order to maintain them in a metabolically fed state on the following day when they were fasted, without preventing the psychological stress associated with fasting. We reasoned that if metabolic signals are responsible for causing the fasting-induced suppression of LH secretion, overfeeding on the day before fasting would prevent the fasting-induced suppression of LH secretion. Eight adult male rhesus monkeys with indwelling venous catheters were studied on three occasions: on a day of normal feeding (receiving approximately 30 pellets of monkey chow at 1100 h on the day of the study), on a day of fasting after a day of normal feeding, and on a day of fasting after a day of overfeeding (receiving one meal of 100 pellets on the day before the study). Pulsatile LH secretion on a day of fasting after a day of normal feeding (0.4 +/- 0.2 pulses/6 h, measured from 1200-1800 h) was significantly suppressed, P < 0.05, compared to a day of normal feeding (1.8 +/- 0.3 pulses/6 h). In contrast, on a day of fasting after a day of overfeeding there was no significant difference in LH secretion measured from 1200-1800 h (1.5 +/- 0.3 pulses/6 h) compared to a day of normal feeding. Overfeeding the day before fasting prevented the normal fasting-induced suppression of plasma T3 concentrations and delayed the normal fasting-induced decline in plasma insulin concentrations. Overfeeding did not prevent the display of agitated behavior that we have previously documented in monkeys when they are fasted. These results support the hypothesis that the signal(s) which suppresses normal LH secretion after brief periods of fasting is related to the metabolic status of the body during the transition from a fed to a fasted state, rather than a function of the psychological state imposed by withholding food.

Animals↗
PubMed1991

Restoration of pulsatile luteinizing hormone secretion after fasting in rhesus monkeys (Macaca mulatta): dependence on size of the refeed meal.

In men and adult male rhesus monkeys brief periods of fasting (i.e. 1-2 days) can often lead to a suppression of hypothalamic-pituitary-testicular axis activity, marked by decreased circulating concentrations of LH, FSH, and testosterone. Refeeding a normal meal can rapidly restore normal secretory patterns of LH and testosterone. To learn more about the nature of the signal that links reproductive hormone secretion to nutrient intake, we examined whether the degree of restoration of pulsatile LH and testosterone secretion after a brief period of fasting is influenced by the size of the refeed meal. Adult male rhesus monkeys had indwelling venous catheters surgically implanted and were maintained on swivel/tether systems for remote collection of blood samples. Monkeys were fasted for 1 day and then on the following day they were refed one of five meals which varied in size and calorie content (i.e. 0 Cal/0 pellets Purina monkey chow; 100 Cal/5 pellets; 200 Cal/10 pellets; 300 Cal/15 pellets; or 600 Cal/30 pellets). Blood samples were collected from 0800-2400 h at 20-min intervals on the days of refeeding and assayed for LH and testosterone content. After a day of fasting, the frequency of pulsatile LH secretion the following morning was very low (0.56 +/- 0.1 pulses/3 h, measured from 0800-1100 h). When monkeys were not refed (i.e. were subjected to a second day of fasting; 0 pellet group) LH pulse frequency remained low [2.88 +/- 0.72 pulses/13 h, measured from 1100-2400 h (equivalent to 0.66 pulses/3 h)] throughout the day and evening hours. Refeeding monkeys 5, 10, 15, and 30 pellets caused a progressive stimulation of pulsatile LH secretion (3.17 +/- 0.54, 3.67 +/- 0.56, 5.5 +/- 0.67, and 6.38 +/- 0.53 pulses/13 h, respectively). Like LH pulse frequency, mean circulating LH and testosterone concentrations progressively increased as the size of the refeed meal was increased. For all three parameters (i.e. LH pulse frequency, mean LH concentration, and mean testosterone concentration) there was a significant, P less than or equal to 0.001, linear trend with increasing meal size. These findings indicate a very strong relation between the level of nutritional intake and the level of central drive to the reproductive axis during nutritional recovery from fasting, and suggest a physiological parameter that responds in a progressive fashion to increasing food intake serves as the signal to link central drive to the reproductive axis to changes in nutrient intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗