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Biomedical subjects

S J Judd

Publications and source records attributed to S J Judd.

At least 37 records · Page 2Linked to original sources
PubMed1987

Evidence against the involvement of opiate neurons in mediating the effect of clomiphene citrate on gonadotropin-releasing hormone neurons.

This study was designed to assess whether the hypothalamic action of clomiphene citrate (CC) on gonadotropin-releasing hormone (GnRH) neurons required activity of opiate neurons. Ten women were studied in two successive cycles. In the first cycle they received infusion of saline or naloxone (2 mg intravenous bolus followed by 1.6 mg/hour) for 9 hours, in random order on days 5 and 6 of the cycle. In the second cycle each woman was treated with CC (100 mg) for 5 days before study on day 6. In each study, blood samples were collected at 15-minute intervals for 9 hours; during the last hour 10 micrograms GnRH was given to test the pituitary response. After CC, luteinizing hormone (LH) pulse frequency was accelerated, and mean serum LH, serum follicle-stimulating hormone, and estradiol increased, but the pituitary response to GnRH was unchanged. These changes are best explained by an increase in activity of GnRH neurons. Conversely, naloxone had no effect on LH pulsatility or the pituitary response to GnRH. This indicates that the action of CC at least during the early follicular phase is exerted primarily at the levels of the hypothalamic GnRH pulse generator and does not depend on the activity of opiate neurons.

Clomiphene↗
PubMed1986

The effect of physiological changes in ovarian steroids on the prolactin response to gonadotrophin releasing factor.

This study was designed to assess the effect of an altered level of serum oestrogen and progesterone on the prolactin (PRL) response to gonadotrophin releasing hormone (GnRH). Six normal women were studied in the early follicular phase and the mid-luteal phase of one cycle and five menopausal women were studied before and after treatment with progesterone. Blood samples were collected at 15 min intervals for 6 h after a basal collection period of 30 min. Intravenous boluses of GnRH (1 microgram, 10 micrograms and 50 micrograms) were given at 0, 2 and 4 h. Basal samples were assayed for 17 beta-oestradiol (E2), oestrone (E1) and progesterone (P); LH, FSH and PRL were measured in all samples. Serum PRL was significantly elevated in all groups after 10 micrograms of GnRH with maximum increments (+/- SEM) ranging from 3.9 +/- 1.3 micrograms/l in early follicular phase women to 14.7 +/- 4.7 micrograms/l in progesterone-treated menopausal women. The PRL response to GnRH was significantly greater in the luteal phase and in menopausal women compared to early follicular phase women. There was a significant correlation between the maximum PRL response and the maximum LH response to GnRH in all the women studied (r = 0.7; P less than 0.01). A significant correlation was also found between the maximum PRL response and the basal serum oestrogen concentration in the normal cycling women (r = 0.8; P less than 0.01), but not when the menopausal women were included in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Role of endogenous opioids in reducing the frequency of pulsatile luteinizing hormone secretion induced by progesterone in normal women.

It is well-established that the frequency of LH pulses varies during the normal menstrual cycle with a significant reduction in frequency in the luteal phase. Previous studies have indicated that both progesterone and opioids are able to reduce the frequency of LH pulses and in this study we sought to clarify the possible interaction between progesterone, endogenous opioids and GnRH neurons. Sixteen normal women in the mid-follicular phase (days 8-12) were randomly allocated to a control or treatment group and LH pulsatility assessed on one or two occasions by taking blood samples at 15 min intervals over 8 h. For the control women, LH pulsatility was assessed on one occasion during a saline infusion. The treated women received progesterone (50-100 mg/d for 7 d) at the end of which LH pulsatility was assessed before and after a naloxone infusion (2 mg/h for 8 h). Mean +/- SEM LH pulse frequency in the control women was 4.9 +/- 0.5 pulses/8 h which was significantly decreased to 3.0 +/- 0.3 pulses/8 h (P less than 0.01) in the progesterone treated women but not different from 5.5 +/- 0.3 pulses/8 h in those also treated with naloxone. Mean +/- SEM LH pulse amplitude in the control women was 2.3 +/- 0.3 IU/l, which was significantly increased to 4.8 +/- 0.7 IU/l (P less than 0.05) in the progesterone treated group, and to 3.7 +/- 0.4 IU/l (P less than 0.05) in the progesterone-treated women after naloxone. We conclude that progesterone slows the frequency of LH pulsatility by increasing endogenous opioid activity in the hypothalamus which may in turn inhibit the firing rate of the GnRH neurons.

Adult↗
PubMed1986

Activity of gonadotropin-releasing hormone neurons during the preovulatory luteinizing hormone surge.

We assessed the frequency of luteinizing hormone (LH) pulsatility (reflecting the activity of gonadotropin-releasing hormone [GnRH] neurons in the hypothalamus) in six women during the periovulatory LH surge, in five women during the early follicular phase, and in seven women in the midfollicular phase (MFP) (calculated as being 3 to 8 days before the LH surge). Collection of blood at 5-minute, versus 15-minute, intervals allowed detection of a larger number of LH pulses in both the MFP (16, versus 27) and periovulatory phase (POP) (11, versus 22) groups of women, but it made no difference in the early follicular phase (EFP) (10 pulses with both methods). During the EFP, the mean number of LH pulses per 4 hours (detected by 5-minute sampling) was 2.0 +/- 0.7 (+/- standard deviation [SD]), and the mean LH amplitude (+/- SD) was 1.3 +/- 0.4 IU/l. There was a significant increase in the number of pulses in the MFP group (3.9 +/- 1.3 pulses/4 hours; P less than 0.05) but no significant change in pulse amplitude (1.1 +/- 0.1 IU/l). During the POP, the mean pulse amplitude was increased (8.5 +/- 1.4 IU/l; P less than 0.001), compared with the MFP and EFP groups, but the mean pulse frequency (3.7 +/- 1.2 pulses/4 hours) was not significantly different from the MFP frequency. We conclude that an acceleration of LH pulsatility occurs several days before the LH surge and does not change thereafter. However, there is an increase in LH pulse amplitude during the LH surge; we attribute this to the increase in pituitary sensitivity at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Regulation of pulsatile secretion of progesterone during the human luteal phase.

This study was designed to evaluate the role of luteinizing hormone (LH) and prolactin (PRL) in regulating pulsatile progesterone secretion in the human. This was done first by correlating the frequency of progesterone, LH and PRL pulses during the mid-luteal phase of normal cycles. Second, by increasing the frequency of LH pulses with naloxone and GnRH injections and examining the impact on progesterone pulse frequency. Third, by abolishing PRL pulsatility with metoclopramide and looking at the effect on progesterone pulsatility. Nine normal subjects in the mid-luteal phase (4-10 days after the initial postovulatory rise in progesterone) were studied for 8 h with blood samples taken at 15 min intervals. Each sample was assayed for progesterone, LH and PRL and the pulse frequency (number of pulses in 8 h) determined for each hormone. The mean pulse frequencies were 2.3 (s.e.m. = 0.4) for progesterone, 1.3 (s.e.m. = 0.4) for LH, and 2.1 (s.e.m. = 0.3) for PRL. Cross-correlation analysis showed that there was no significant synchrony between pulses of progesterone and pulses of LH and PRL. When naloxone was given to six normal subjects in the mid-luteal phase, the mean LH pulse frequency (number of pulses in 6 h) was increased from 2.2 (s.e.m. = 0.3) during a saline infusion to 3.2 (s.e.m. = 0.5) during the naloxone infusion (P less than 0.05). However, the mean pulse frequency for progesterone remained unchanged during the saline and naloxone studies. There was no significant difference between the mean serum LH in the saline and naloxone groups, and the mean serum progesterone concentration was not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Responses to prolactin secretagogues in oestrogen-treated rats suggest that the defect in prolactin regulation produced by oestrogen is at the level of the pituitary gland.

Prolactin responses to pharmacological agents were used to characterize the defect in prolactin regulation which occurs after administration of high doses of oestrogen to rats. Animals with chronically implanted venous cannulae were injected with 2 mg oestradiol benzoate in oil and 2-3 days later prolactin concentrations were measured after injections of saline, thyrotrophin-releasing hormone (TRH), fenfluramine, apomorphine and butaclamol. The responses were compared with those in oil-injected animals. Hyperprolactinaemia in oestrogen-treated animals was unresponsive to apomorphine, but was even more sensitive to dopamine receptor blockade than controls. These results suggest that the lactotrophs in oestrogen-treated animals are already maximally suppressed by endogenous dopamine, though ineffectively. Although there was an increased prolactin response to TRH in oestrogen-treated animals, there was an impaired response to fenfluramine, indicating suppressed serotonergic prolactin-releasing factor mechanisms. Maximal endogenous dopaminergic activity and suppressed prolactin-releasing factor mechanisms are appropriate hypothalamic responses to hyperprolactinaemia. The operation of these responses in the earliest stages of the development of pituitary hyperplasia indicates that oestrogen induces a disturbance of prolactin regulation in the lactotroph, independent of hypothalamic control.

Animals↗
PubMed1985

Reliability of a single serum progesterone determination as an indicator of ovulation.

Nine normal cycling subjects were monitored for mid-cycle LH surge and a subsequent rise in serum progesterone levels. Frequent samples were then taken for progesterone measurement during 8 h sessions in the early, mid and late luteal phases. These data showed: that progesterone secretion is pulsatile throughout the human luteal phase, with maximum frequency in the mid-luteal phase; that during the mid-luteal phase most subjects had progesterone levels both above and below currently accepted ovulatory thresholds; the use of a single measurement of progesterone in the mid-luteal phase is not always a reliable indicator of ovulation; a threshold greater than 20 nmol/l may yield an unacceptable number of false negative results.

Adult↗
PubMed1984

Synchronous secretion of luteinizing hormone and prolactin in the human luteal phase: neuroendocrine mechanisms.

Studies of normal luteal phase women have shown that increases in serum LH and PRL are commonly synchronous. This study was designed to investigate the possible neuroendocrine mechanism(s) underlying this phenomenon. Six normal women were studied during the midluteal phase of 2 cycles. In the first cycle, they had blood samples collected at 15-min intervals for 6 h on 3 occasions during which time they received an infusion of normal saline or naloxone (1 mg/h) or a bolus of metoclopramide (10 mg, iv). In a second cycle, they received GnRH in increasing iv doses of 1, 10, and 50 micrograms at 2-h intervals. During the saline infusion, 11 of the 16 serum LH pulses (69%) were accompanied by an increase in serum PRL, and in 5 of the subjects, the first pulse of LH was synchronous with that of PRL (P = 0.0015). Naloxone increased the number of LH pulses from 16 to 20 and the number of PRL pulses from 12 to 16, all of which were synchronous with LH pulses. Administration of metoclopramide caused a substantial increase in PRL and a loss of further PRL pulsatility; however, LH pulsatility remained unaffected. Even after the smallest dose of GnRH (1 microgram), there was an increase in serum PRL [basal level, 11.8 +/- 2.1 (+/- SE) micrograms/liter; peak level, 16.5 +/- 3.3 micrograms/liter] as well as LH and FSH. The increase in serum PRL was, unlike the gonadotropin response, maximal after the 10-microgram dose of GnRH (peak level, 23.2 +/- 6 micrograms/liter) and did not increase further after the 50-micrograms dose (peak level, 18.5 +/- 2.4 micrograms/liter). These studies demonstrate that there is a PRL response to GnRH in the luteal phase and suggest that the observed synchrony in LH and PRL secretion at this time results from a physiological response of both the gonadotrope and the lactotrope to endogenous GnRH.

Adolescent↗
PubMed1983

Influence of prolactin on serum androgens in normoprolactinaemic women.

Previous studies in hyperprolactinaemic women have led to conflicting views about the influence of prolactin (PRL) on serum dehydroepiandrosterone sulphate (DS) levels. This study was designed to examine the effect of a reduction of normal levels of circulating prolactin on the serum DS concentration in twenty ovulating women treated with bromocriptine for 4 months in a double-blind crossover study. The women were recruited after initial studies of hypothalamic-pituitary, gonadal and adrenal function were assessed as being normal. Blood samples were collected in the early follicular and mid-luteal phases of both placebo and bromocriptine treated cycles, and were assayed for LH, FSH, PRL, DS, oestradiol (E2), testosterone (T), androstenedione (A) and sex hormone binding globulin (SHBG). The only significant changes were in serum prolactin which decreased from a mean level of 12.6 (s.e.m. = 0.38) to 9.7 (s.e.m. = 0.36) micrograms/l (P less than 0.0025), and DS which decreased from 4.9 (s.e.m. = 0.23) to 4.5 (s.e.m. = 0.22) mumol/l (P much less than 0.0005) after treatment with bromocriptine. Although the mechanism of this phenomenon is not clear, this study suggests that PRL may have a physiological role in modulating the tonic secretion or metabolism of DS.

Adult↗
PubMed1979

Effects of a dopamine antagonist on the release of gonadotropin and prolactin in normal women and women with hyperprolactinemic anovulation.

Administration of a dopamine (DA) antagonist, metoclopramide (MCP) resulted in dose-related acute increments of circulating levels of LH and FSH in patients with hyperprolactinemic anovulation due to pituitary microadenoma but not in normal cycling women during the early follicular phase. Concomitant PRL responses to MCP in hyperprolactinemic patients were 1/10 those observed in the cycling women. These findings suggest a relative DA excess at the hypothalamic LRF neurons and a relative DA deficiency at the adenoma lactotroph of hyperprolactinemic patients as compared to cycling women.

Adenoma↗
PubMed1979

The effects of ovariectomy and estrogen treatment on the dopamine inhibition of gonadotropin and prolactin release.

The suppressive action of dopamine (DA) on circulating gonadotropin and PRL levels is found to be positively correlated with their basal serum concentrations. Thus, DA inhibition is greater in ovariectomized (agonadal) women than in normal women on day 2 of their menstrual cycles, and the reverse is observed for PRL. Pretreatment of agonadal subjects with estrogen lowers the basal levels of LH and FSH and thereby proportionately decreases the suppressive effects of DA. Estrogen treatment elevates the basal level of PRL in agonadal subjects and also the PRL-inhibiting effect of DA. These findings indicate that castration and estrogen treatment significantly influence the inhibitory effect of DA on gonadotropin and PRL release.

Adult↗
PubMed1978

Inhibition of gonadotropin and prolactin release by dopamine: effect of endogenous estradiol levels.

The influence of endogenous estradiol (E2) levels on gonadotropin and PRL sensitivity to dopamine (DA) infusion (4 micrograms/kg/min) was assessed at different stages of the follicular phase of the menstrual cycle. Basal LH and FSH levels were comparable in day 2 and day 12 subjects, and despite a 4-fold increase in E2 concentration, the inhibition of LH by DA was small and quantitatively similar and there was no discernible effect on FSH in either group. In marked contrast, day 14 subjects with an elevated basal LH level exhibited a dramatic increase in the sensitivity of LH and FSH to DA inhibition. Further, a remarkable rebound release for LH but not FSH occurred on the termination of DA infusion. There was a significant correlation between basal LH and response to DA (r = 0.979). This unique increase in response to DA at a time when hypothalamic LRF secretion is assumed to be elevated suggests that DA may exert its effect by inhibiting LRF release. The inhibition of PRL release by DA is correlated with endogenous E2 levels (r equal 0.685) as well as basal PRL levels (r = 0.878). Rebound release of PRL occurs in all three groups of women on termination of the DA infusion, but the magnitude was greatest in Day 14 subjects with the highest endogenous E2 levels. These data suggest that while E2 seems to augment the sensitivity of PRL inhibition by DA, its does not seem to directly influence gonadotropin sensitivity to DA inhibition. The selective hypersensitivity of both LH and FSH to DA observed on the day before midcycle LH peak is consistent with a reduction in LRF neuronal inhibition by tuberoinfundibular DA neurons at this time.

Dopamine↗
PubMed1976

Hyperprolactinaemia: its physiology and investigation.

Since the establishment of a sensitive and specific radioimmunoassay for serum prolactin levels, very rapid progress has been made in the understanding of the physiology of prolactin and its role in human disease. Hyperprolactinaemia is now known to be a common finding in many conditions. Up to 20% of women with unexplained functional secondary amenorrhoea have an elevated serum prolactin level. Reduction of serum prolactin levels to normal, by removal of a prolactin-secreting tumour or by treatment with bromoergocryptine, results in a restoration of normal menstrual cycles and fertility. This paper outlines the control of prolactin secretion and discusses the mechanisms which result in secondary amenorrhoea. A new method of investigation of hyperprolactinaemia is proposed which localizes the site of abnormality which results in an elevation of serum prolactin levels.

Adenoma, Chromophobe↗