Neurohypophysial secretion to insulin-induced hypoglycemia and its regulation by endogenous opioids in women

1990 ◽  
Vol 122 (4) ◽  
pp. 467-471 ◽  
Author(s):  
Mark R. Johnson ◽  
Mark Bower ◽  
Jonathan R. Seck ◽  
Stafford L. Lightman

Abstract. In animals, there is sexual dimorphism of both neurohypophysial peptide secretion in response to stressful stimuli and to the inhibitory effects of opioids. In men, endogenous opioids inhibit the release of oxytocin when AVP secretion is stimulated by insulin-induced hypoglycemia. We have now investigated the role of endogenous opioids in the AVP and oxytocin response to insulin-induced hypoglycemia in women. Twelve subjects, 6 in the follicular and 6 in the luteal phase of the menstrual cycle, were infused on 2 occasions with naloxone (4 mg bolus and 6 mg/h) or saline. Soluble insulin (Human Actrapid®, 0.15 μ/kg, iv) was given and serial blood samples taken. Blood sugar fell significantly (p<0.05) and similarly in all groups. In the follicular phase hypoglycemia led to a rise in plasma AVP from 1.3 ± 0.2 to 1.8 ± 0.2 pmol/l in the saline-infused subjects (NS), and from 1.0 ± 0.1 to 2.0 ± 0.2 pmol/l in the naloxone-infused (p<0.05). AVP rose similarly from 0.6 ± 0.1 to 1.6 ± 0.5 pmol/l (p<0.05) in the luteal phase controls and from 0.8 ± 0.1 to 1.5 ± 0.3 pmol/l (p<0.05) in naloxone-infused subjects in the luteal phase. There were no significant differences between any of these groups. There were no significant changes in plasma oxytocin in any group. We therefore conclude that in women, unlike men, endogenous opioids do not modulate oxytocin or vasopressin release during insulin-induced hypoglycemia.

2000 ◽  
Vol 166 (1) ◽  
pp. 39-44 ◽  
Author(s):  
S Jarvis ◽  
AB Lawrence ◽  
KA McLean ◽  
J Chirnside ◽  
LA Deans ◽  
...  

Oxytocin plays an important role at parturition due to its involvement in uterine contractions, foetal expulsion and the onset of maternal behaviour. The role of the related neurohypophysial hormone, vasopressin, is less clear; however, there is some evidence that it is also involved in maternal behaviour and its role in osmotic regulation is well established. The aim of this study was to investigate the inhibitory effects of endogenous opioids on these hormones during the expulsive phase of parturition in the pig, and to examine how opioid restraint interacts with environmental restriction. The subjects of this study were 31 Large Whitex Landrace primiparous sows (gilts). An indwelling jugular catheter was implanted under general anaesthesia at 12 days before the expected parturition day (EPD). From 5 days before the EPD 15 of the gilts were individually housed in a restrictive parturition crate without straw and 16 were individually housed in a straw-bedded pen. Blood samples were taken with increasing frequency towards and during parturition through a catheter extension to reduce disturbance. At 7.5 min after the birth of the first piglet half of the gilts in each environment received a dose of the opioid receptor antagonist naloxone (1 mg/kg, i.v.) with the remaining gilts receiving saline as a control. Overall, there was no effect of environment on either circulating oxytocin or vasopressin. However, both oxytocin and vasopressin were inhibited by endogenous opioids during the expulsive phase. The inhibitory effects of opioids on these hormones did not appear to have any adverse effects on the progress of parturition as judged by cumulative piglet birth intervals. The regulation of the opioid inhibition of oxytocin and vasopressin during parturition is discussed in relation to other neurotransmitters and whether opioid inhibition of these neurohypophysial hormones is part of the 'normal' physiological response to parturition or whether it is stress-induced.


1988 ◽  
Vol 118 (1) ◽  
pp. 77-81 ◽  
Author(s):  
J. R. Seckl ◽  
J. A. Haddock ◽  
M. J. Dunne ◽  
S. L. Lightman

Abstract. We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulininduced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P < 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Salineinfused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 ± 0.4 pmol/l before insulin to 3.2 ± 1.3 pmol/l at 45 min (P < 0.05). We conclude that there is opioidmediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.


1981 ◽  
Vol 240 (5) ◽  
pp. E489-E492
Author(s):  
J. A. Resko ◽  
W. E. Ellinwood ◽  
E. Knobil

To obtain new information on the site of the inhibiting actions of progesterone (P) during the follicular phase of the cycle, we administered P continuously to 13 rhesus macaques (Macaca mulatta) from days 5 through 12 of the menstrual cycle. This treatment produced luteal-phase levels (approximately 6 ng/ml of serum) within 4 h. (FSH) concentrations dropped significantly from pretreatment amounts (P less than 0.01). During this time, both immunoreactive luteinizing hormone (LH) (n = 8 animals) and bioactive LH (n = 5) remained stable. The 17 beta-estradiol (E2) concentrations dropped significantly below base line 24 h after treatment (P less than 0.05). The decline in E2 occurred after the decline in FSH. Inhibition of FSH continued for 40 h, after which both FSH and LH rose steadily in a way that resembled a preovulatory surge on days 8 or 9 of the menstrual cycle, and then returned to base line by day 10. When gonadotropins were at their zenith, the ovary did not respond by secreting E2. None of the effects mentioned above were found in control animals treated with blank implants. These data demonstrate that P administered during the follicular phase inhibits FSH but not LH secretion. This initial inhibition probably occurs at a hypothalamic-pituitary site, but after 40 h direct inhibitory effects on the ovary cannot be ruled out. P stimulates the release of gonadotropin in female monkeys despite reduced production of E2 by the ovary.


SLEEP ◽  
2019 ◽  
Vol 43 (2) ◽  
Author(s):  
Leilah K Grant ◽  
Joshua J Gooley ◽  
Melissa A St Hilaire ◽  
Shantha M W Rajaratnam ◽  
George C Brainard ◽  
...  

Abstract Study objectives Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and their ratio (P4/E2), which change across the menstrual cycle. We examined the role of P4/E2 in modulating performance during extended wake in premenopausal women. Additionally, we compared the acute effects of nighttime light exposure on performance, CBT, and hormones between the menstrual phases. Methods Participants were studied during a 50 h constant routine and a 6.5 h monochromatic nighttime light exposure. Participants were 16 healthy, naturally cycling women (eight follicular; eight luteal). Outcome measures included reaction time, attentional failures, self-reported sleepiness, CBT, melatonin, P4, and E2. Results As compared to women in the luteal phase, women in the follicular phase exhibited worse performance overnight. CBT was significantly associated with performance, P4, and P4/E2 but not with other sex hormones. Sex hormones were not directly related to performance. Light exposure that suppressed melatonin improved performance in the follicular phase (n = 4 per group) to levels observed during the luteal phase and increased CBT but without concomitant changes in P4/E2. Conclusions Our results underscore the importance of considering menstrual phase when assessing cognitive performance during sleep loss in women and indicate that these changes are driven predominantly by CBT. Furthermore, this study shows that vulnerability to sleep loss during the follicular phase may be resolved by exposure to light.


1992 ◽  
Vol 133 (3) ◽  
pp. 381-391 ◽  
Author(s):  
G. E. Mann ◽  
B. K. Campbell ◽  
A. S. McNeilly ◽  
D. T. Baird

ABSTRACT The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1–26α peptide fragment of porcine inhibin and/or oestradiol-17β. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals. After ovariectomy there was a large rise in the peripheral concentration of LH (P < 0·001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post-castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P < 0·001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P < 0·01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P< 0·01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P < 0·01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group. These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone. Journal of Endocrinology (1992) 133, 381–391


Cephalalgia ◽  
1996 ◽  
Vol 16 (6) ◽  
pp. 427-430 ◽  
Author(s):  
L. Fioroni ◽  
G D'Andrea ◽  
M Alecci ◽  
A Cananzi ◽  
F Facchinetti

In order to understand the possible 5-hydroxytryptamine (5HT) anomalies in migraine, particularly in the period before the headache attack, we compared the levels of 5HT, its stable metabolite 5-hydroxyindoleacetic acid (5HIAA) and platelet monoaminoxidase (MAO) activity in patients with menstrual migraine with those of healthy female controls. In every subject, blood samples were drawn during both follicular and late luteal phases of the menstrual cycle. In controls, platelet 5HT levels remained stable, whereas 5HIAA levels and MAO activity were higher in the luteal than in the follicular phase, suggesting an increased catabolism of 5HT which occurs physiologically just before menses. In menstrual migraine 5HIAA levels and MAO activity showed similar changes with higher values in the luteal than in the follicular phase. The luteal phase values were significantly higher than those of controls. Also, and in contrast to controls, 5HT levels decreased in the luteal phase. These data suggest that 5HT availability is reduced in menstrual migraine, possibly due to an increased catabolism and/or to a reduced synthesis, and hence predisposes patients to migraine attacks.


1990 ◽  
Vol 126 (3) ◽  
pp. 385-393 ◽  
Author(s):  
B. K. Campbell ◽  
G. E. Mann ◽  
A. S. McNeilly ◽  
D. T. Baird

ABSTRACT The pattern of pulsatile secretion of inhibin, oestradiol and androstenedione by the ovary at different stages of the oestrous cycle in sheep was studied in five Finn–Merino ewes in which the left ovary had been autotransplanted to the neck. The ewes had jugular venous blood samples collected at 4-hourly intervals from 42 h before the induction of luteolysis by i.m. injection of cloprostenol (100 μg) on day 10 of the oestrous cycle, until day 3 of the following cycle. There were five periods of intensive blood sampling, when both ovarian and jugular venous blood samples were collected, as follows: (a) mid-luteal phase, before the second injection of cloprostenol on day 10 (15-min intervals for 6 h); (b) early follicular phase, 24 h after the second injection of cloprostenol (10-min intervals for 4 h); (c) late follicular phase, 48 h after the second injection of cloprostenol (10-min intervals for 4 h); (d) after the LH surge on day 1 of the cycle, 76 h after the second injection of cloprostenol (10-min intervals for 4 h); (e) early luteal phase on day 3 of the cycle, 120 h after the second injection of cloprostenol (10-min intervals for 3 h). Plasma was collected and the samples assayed for LH, FSH, progesterone, oestradiol, androstenedione and inhibin. The ovarian secretion rates for oestradiol, androstenedione and inhibin were calculated. All ewes responded normally to the luteolytic dose of cloprostenol with the preovulatory surge of LH occurring within 56·4±1·6 h (mean ± s.e.m.) followed by the establishment of a normal luteal phase. The pulse frequency of LH, oestradiol and androstenedione increased in the transition from the luteal to the follicular phase (P<0·01). On day 1 of the cycle LH secretion consisted of low-amplitude high-frequency pulses (1·0±0·1 pulse/h) to which androstenedione, but not oestradiol, responded. On day 3 of the cycle LH secretion was similar to that on day 1 but both androstenedione and oestradiol secretion were pulsatile in response to LH, indicating the presence of oestrogenic follicles. The stage of the cycle had no significant effects on LH pulse amplitude and nadir but the ovarian secretory response to LH stimulation did vary with the stage of the cycle. Prolactin pulse frequency, amplitude and nadir were higher (P<0·05) during the follicular phase than the luteal phase. Prolactin pulse frequency was depressed (P<0·05) on day 1 of the cycle but increased to follicular phase levels on day 3. Prolactin pulse frequency was significantly correlated to oestradiol pulse frequency (r = 0·54; P<0·01). During the luteal phase there were insufficient oestradiol pulses to obtain an estimate of pulse amplitude and nadir but both these parameters reached their highest level during the late follicular phase, fell to negligible levels on day 1 and increased to early follicular phase levels on day 3. Androstenedione pulse amplitude and nadir exhibited similar but less marked variation. Inhibin secretion was episodic at all stages of the cycle examined but did not exhibit significant variation with stage of cycle in any of the parameters of episodic secretion measured. Inhibin pulses were not related to either LH or prolactin at any stage of the cycle. FSH secretion was not detectably pulsatile but jugular venous concentrations of FSH at each stage of the oestrous cycle were negatively correlated with mean oestradiol (r= −0·52; P<0·01 but not inhibin secretion (r = 0·19). We conclude that (i) LH secretion is pulsatile at all stages of the oestrous cycle but the steroidogenic responses of the ovary varies with the stage of the cycle, reflecting changes in characteristics of the follicle population, (ii) ovarian inhibin secretion is episodic and displays little change with the stage of the oestrous cycle and (iii) episodic inhibin secretion is not related to either pulses of LH or prolactin. The aetiology of these inhibin pulses therefore remains unknown. Journal of Endocrinology (1990) 126, 385–393


1980 ◽  
Vol 25 (4) ◽  
pp. S75-S81
Author(s):  
J. R. T. Coutts ◽  
R. Fleming ◽  
M. C. Macnaughton

Daily plasma analysis of complete menstrual cycles from infertile women (n = 32) revealed transient hyperprolactinaemia in a significant number in comparison with normally cycling women. The prolactin elevations occurred for variable durations at different stages of the cycle. Transient hyperprolactinaemia occurring at mid-cycle was associated with reduced late luteal phase steroid levels and short luteal phases. When the prolactin elevations occurred at other times they were unrelated to ovarian steroid levels. Treatment of patients with short luteal phases with bromocriptine (2.5 mg/day) normalised prolactin levels but also reduced gonadotrophins. The net result of these changes was a normalisation of the length of the luteal phase which was now deficient in steroid secretion. To alleviate these problems the treatments proposed for the short luteal phase are either bromocriptine (2.5 mg/day) for 7 days over the mid-cycle period only or bromocriptine for 7 days at mid-cycle in conjunction with a follicular stimulant in the early follicular phase.


1996 ◽  
Vol 149 (3) ◽  
pp. 531-540 ◽  
Author(s):  
B K Campbell ◽  
R J Scaramuzzi

Abstract Recombinant human inhibin A (rhInh) or steroid-free bovine follicular fluid (bFF) were infused into the ovarian artery of anoestrous ewes with ovarian autotransplants induced to ovulate with a pulsatile regimen of GnRH applied after a 10-day pretreatment with progestagen sponges. In the period 12–24 h after sponge withdrawal ewes received ovarian arterial infusions of saline (n=6), 0·3 μg rhInh/h (n=5), 1·6 μg rhInh/h (n=5) or 25 μl bFF/h (n=4). Controls had a normal follicular phase with an LH surge 43 ± 3 h after sponge withdrawal which resulted in ovulation (six out of six). Both doses of rhlnh increased ovarian venous inhibin concentrations in a dose-related fashion (P<0·05) but resulted in depressions (P<0·05) in FSH concentrations of similar magnitude. Both doses of rhInh acutely inhibited ovarian oestradiol and androstenedione secretion (P<0·01) but at the end of rhInh infusion oestradiol secretion was quickly re-established without a corresponding increase in FSH. LH surges were detected in five out of five and three out of five ewes infused with low and high doses of rhInh respectively, and progesterone concentrations during the subsequent luteal phase were depressed (P<0·05). Infusion of bFF had no effect on inhibin or FSH concentrations but resulted in acute inhibition (P<0·01) of ovarian oestradiol, androstenedione and inhibin secretion, a delay (P<0·05) in the time to the LH surge and a depression (P<0·05) in luteal-phase progesterone concentrations. In conclusion, while the depression in FSH induced by rhlnh cannot be excluded as a cause for the inhibitory effects of rhInh treatment on ovarian function, such a mechanism cannot fully explain the ovarian responses obtained to rhInh infusion. These results therefore support a direct ovarian role for inhibin in the modulation of ovarian function in addition to its indirect role in controlling FSH. This conclusion is supported by the demonstration that bFF can induce similar inhibitory effects on ovarian function without changing FSH. Journal of Endocrinology (1996) 149, 531–540


2003 ◽  
Vol 49 (1) ◽  
pp. 41-44
Author(s):  
S. V. Shirshev ◽  
O. G. Lyalina

The effect of chorionic gonadotropin (CG) on intracellular po­tassium ion( [K+]) levels in human blood immunocompetent cells was studied by taking into account the phases of a menstrual cy­cle. CG was used in doses of 10, 50, and 100 IU/ml. Plasma photometry was used to measure the level of [K+] ‘ in the frac­tionated peripheral monocytes and lymphocytes from males, as well as from females in the late follicular and luteal phases of a menstrual cycle. CG used in a dose of 100 IU/ml was found to lower flCf in the monocytes and lymphocytes of males and in a dose of 50 IU in the lymphocytes of females in the luteal phase of a menstrual cycle. The hormone used in large doses stabilized the level of [K+] in both types of cell of female in the follicular phase. It is concluded that CG can modulate the level of [K+] in human peripheral blood immunocompetent cells, and the direc­tionality of its effects depends on a type of hormone-accepting cells and it is determined by a menstrual phase.


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