The role of intracerebral insulin in the effect of nutrition on gonadotrophin secretion in mature male sheep

1995 ◽  
Vol 147 (2) ◽  
pp. 321-329 ◽  
Author(s):  
D W Miller ◽  
D Blache ◽  
G B Martin
Keyword(s):  
Live Weight ◽  
Nutritional Supplement ◽  
Pulse Frequency ◽  
Plasma Prolactin ◽  
Gnrh Secretion ◽  
Gonadotrophin Secretion ◽  
Metabolic Signal ◽  
Lh Secretion ◽  
Male Sheep

Abstract The effect of nutrition on gonadotrophin secretion may be exerted through a central metabolic signal that reflects nutritional status. We have previously found that glucose and insulin concentrations are elevated in the cerebrospinal fluid (CSF) of rams in which the secretion of gonadotrophins has been stimulated by a nutritional supplement of lupin grain (Lupinus angustifolius). In the present study, we tested the hypothesis that insulin and/or glucose is a metabolic modulator of GnRH secretion and mediates the effects of nutrition on gonadotrophin secretion. Six mature rams were fed a diet that maintained live weight and then given a series of infusions, each for 12 h/day for 4 days, in a cross-over design. The treatments were: artificial CSF (aCSF), glucose (50 μmol/h) in aCSF, insulin (0·6 ng/h) in aCSF, and glucose (50 μmol/h) plus insulin (0·6 ng/h) in aCSF; all infused at a rate of 5 μl/min. At the same time as the infusion treatments, two other groups of four rams without cerebral cannulae were fed either the maintenance diet or the same diet supplemented with 750 g lupin grain per head per day for 4 days, again in a cross-over design. Rams fed the lupin supplement showed an increase in both LH pulse frequency and mean FSH on day 4 (P<0·05). Infusion of aCSF or glucose did not affect gonadotrophin secretion. Rams infused with insulin or insulin plus glucose showed an increase (P<0·05) in LH pulse frequency but no increase in FSH concentrations on day 4 of infusion. The magnitude of the LH response to insulin was similar to the nutritional response of feeding lupin supplements. There was no effect of any of the infusion treatments on plasma prolactin or insulin secretion. These data show that changes in insulin concentrations in the CSF lead to changes in LH secretion and support the hypothesis that insulin is a metabolic modulator of GnRH secretion and mediates the effects of nutrition on gonadotrophin secretion. Journal of Endocrinology (1995) 147, 321–329

Role of peripheral and central aromatization in the control of gonadotrophin secretion in the male sheep

1999 ◽  
Vol 11 (5) ◽  
pp. 293 ◽  
Author(s):  
T. P. Sharma ◽  
D. Blache ◽  
M. A. Blackberry ◽  
G. B. Martin
Keyword(s):  
Third Ventricle ◽  
Pulse Frequency ◽  
Major Site ◽  
The Third ◽  
Artificial Cerebrospinal Fluid ◽  
Gonadotrophin Secretion ◽  
Lh Secretion ◽  
Plasma Oestradiol ◽  
Male Sheep

Both testosterone and its aromatized metabolite, oestradiol-17b, are known to act centrally on the secretion of GnRH, but the major site of aromatization is not clear as aromatase activities are found in numerous tissues including brain and testis. Here, we tested the importance of central aromatization of testosterone using a non-steroidal aromatase inhibitor, fadrozole. To distinguish between testicular and non-testicular sites, five intact and five testosterone-infused castrated rams (600 g kg –1 per 24 h for 3 days) were given four injections of fadrozole (i.m; 500 g kg –1 ) at 48, 52, 64 and 68 h relative to the start of testosterone infusion. Control rams (n = 5) received vehicle only. Fadrozole treatment decreased plasma oestradiol-17b concentrations and increased the LH pulse frequency in both intact rams and testosterone-treated castrates, suggesting that non-testicular sites of aromatization are important in the control of pulsatile LH secretion. To test the importance of central aromatization, intact rams (n = 5) were infused into the third ventricle with vehicle (artificial cerebrospinal fluid) or with fadrozole (20 and 200 g kg –1 per day). After two weeks, the same two doses of fadrozole were infused intravenously instead of intracerebrally. Central infusion of fadro-zole did not affect plasma oestradiol concentrations but increased LH pulse frequency. Only the highest dose increased LH pulse frequency when infused intravenously. In conclusion, central aromatization is involved in the control of pulsatile LH secretion in male sheep.

Interactions between nutrition, testosterone and inhibin in the control of gonadotrophin secretion in mature rams

1996 ◽  
Vol 8 (5) ◽  
pp. 855 ◽  
Author(s):  
S Tjondronegoro ◽  
GB Martin ◽  
SR Sutherland ◽  
R Boukhliq
Keyword(s):  
Plasma Concentrations ◽  
Dietary Treatment ◽  
Plasma Testosterone ◽  
Group V ◽  
Intermediate Group ◽  
Gonadotrophin Secretion ◽  
The Mean ◽  
Lh Secretion ◽  
Male Sheep

The role of negative feedback by two testicular hormones, testosterone and inhibin, in the gonadotrophin responses of mature male sheep to changes in nutrition was tested. Six days after castration, 24 Merino rams were assigned to groups that were fed either a diet that maintained their initial liveweight (Intermediate diet), or about half of the Intermediate diet (Low diet), or the Intermediate diet with a supplement of lupin grain (High diet). One week after the change of diet, all animals were given subcutaneous testosterone implants, providing plasma testosterone concentrations of 3.06 +/- 0.14 ng mL-1 (mean +/- s.e.m.; n = 24). The implants were left in place for 7 days, during which time all the rams were also injected subcutaneously with 2 mL steroid-free bovine follicular fluid (bFF) every 8 h, to provide inhibin at mean plasma concentrations of 0.40 +/- 0.04 ng mL-1 (n = 24; compared with 1.50 +/- 0.12 ng mL-1 when the animals were intact). Five days after castration, there were significant increases in the frequency of luteinizing hormone (LH) pulses (from 1.83 +/- 0.23 to 17.3 +/- 0.96 pulses per 12 h; mean +/- s.e.m.; n = 24) and concentrations of FSH (from 0.45 +/- 0.07 to 14.19 +/- 2.7 ng mL-1; n = 24). Dietary treatment did not significantly affect these responses. Treatment with bFF and testosterone for 7 days reduced LH-pulse frequencies and follicle-stimulating hormone (FSH) concentrations in all groups. The degree of reduction was least in the group on the High diet, for which the FSH concentration (6.49 +/- 1.96 ng mL-1) and frequency of LH pulses (7.00 +/- 2.31 pulses per 24 h) were significantly higher than those observed in the other groups. The mean frequency of LH pulses did not differ significantly between the Intermediate group (0.88 +/- 0.61 pulses per 24 h) and the Low group (0.25 +/- 0.25 pulses per 24 h). Similarly, FSH concentrations did not differ significantly between these two groups (1.78 +/- 0.46 for the Intermediate group v. 1.33 +/- 0.26 ng mL-1 for the Low group). It is concluded that there is no response to diet in the absence of testicular hormones and the effects of nutrition on LH secretion in castrated rams given exogenous testosterone and inhibin are similar to those observed in intact rams.

The role of oestrogens on gonadotrophin secretion in the testicular feminization syndrome1

1980 ◽  
Vol 95 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Martha Medina ◽  
Alfredo Ulloa-Aguirre ◽  
Maria A. Fernández ◽  
Gregorio Pérez-palacios
Keyword(s):  
Clomiphene Citrate ◽  
Poor Response ◽  
Testicular Feminization ◽  
Normal Response ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Before And After ◽  
Complete Form ◽  
Lh Secretion

Abstract. The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after I.RH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following I.RH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects. Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed. These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.

scholarly journals Kisspeptin and neurokinin B interactions in modulating gonadotropin secretion in women with polycystic ovary syndrome

2020 ◽  
Vol 35 (6) ◽  
pp. 1421-1431
Author(s):  
Karolina Skorupskaite ◽  
Jyothis T George ◽  
Johannes D Veldhuis ◽  
Robert P Millar ◽  
Richard A Anderson
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Clinical Research ◽  
Polycystic Ovary ◽  
Pulse Frequency ◽  
Research Facility ◽  
Neurokinin B ◽  
Ovary Syndrome ◽  
Clinical Research Facility ◽  
Lh Secretion

Abstract STUDY QUESTION What is the role of the hypothalamic neuropeptide neurokinin B (NKB) and its interaction with kisspeptin on GnRH/LH secretion in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Administration of neurokinin 3 receptor antagonist (NK3Ra) for 7 days reduced LH and FSH secretion and LH pulse frequency in women with PCOS, whilst the stimulatory LH response to kisspeptin-10 was maintained. WHAT IS KNOWN ALREADY PCOS is characterized by abnormal GnRH/LH secretion. NKB and kisspeptin are master regulators of GnRH/LH secretion, but their role in PCOS is unclear. STUDY DESIGN, SIZE, DURATION The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7). On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion. This was repeated with the alternate infusion in a subsequent cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects were women with PCOS, studied in a Clinical Research Facility. Reproductive hormones were measured before and after NK3Ra administration. On the last day of NK3Ra administration (or the equivalent cycle day in untreated women), all women attended for an 8-h frequent blood sampling to allow analysis of the pulsatile LH secretion. MAIN RESULTS AND THE ROLE OF CHANCE NK3Ra reduced LH secretion (4.0 ± 0.4 vs 6.5 ± 0.8 IU/l, P &lt; 0.05) and pulse frequency (0.5 ± 0.1 vs 0.8 ± 0.1 pulses/h, P &lt; 0.05); FSH secretion was also reduced (2.0 ± 0.3 vs 2.5 ± 0.4 IU/l, P &lt; 0.05). Without NK3Ra pre-treatment, kisspeptin-10 increased LH secretion (5.2 ± 0.5 to 7.8 ± 1.0 IU/L, P &lt; 0.05), with a positive relationship to oestradiol concentrations (r2 = 0.59, P &lt; 0.05). After NK3Ra administration, the LH response to kisspeptin-10 was preserved (vehicle 3.5 ± 0.3 vs 9.0 ± 2.2 IU/l with kisspeptin-10, P &lt; 0.05), but the positive correlation with oestradiol concentrations was abolished (r2 = 0.07, ns. after NK3Ra). FSH secretion was increased by kisspeptin-10 after NK3Ra treatment, but not without NK3Ra treatment. LIMITATIONS, REASONS FOR CAUTION The study did not explore the dose relationship of the effect of NK3R antagonism. The impact of obesity or other aspects of the variability of the PCOS phenotype was not studied due to the small number of subjects. WIDER IMPLICATIONS OF THE FINDINGS These data demonstrate the interactive regulation of GnRH/LH secretion by NKB and kisspeptin in PCOS, and that the NKB system mediates aspects of oestrogenic feedback. STUDY FUNDING/COMPETING INTEREST(S) Wellcome Trust through Scottish Translational Medicine and Therapeutics Initiative (102419/Z/13/A) and MRC grants (G0701682 to R.P.M. and R.A.A.) and MR/N022556/1 to the MRC Centre for Reproductive Health. This work was performed within the Edinburgh Clinical Research Facility. J.T.G. has undertaken consultancy work for AstraZeneca and Takeda Pharmaceuticals and is an employee of Boehringer Ingelheim. R.P.M. has consulted for Ogeda and was CEO of Peptocrine. R.A.A. has undertaken consultancy work for Merck, Ferring, NeRRe Therapeutics and Sojournix Inc. J.D.V. and K.S. have nothing to disclose. TRIAL REGISTRATION NUMBER N/A.

Effects of oestradiol, progesterone and androstenedione on the pulsatile secretion of luteinizing hormone in ovariectomized ewes during spring and autumn

1983 ◽  
Vol 96 (2) ◽  
pp. 181-193 ◽  
Author(s):  
G. B. Martin ◽  
R. J. Scaramuzzi ◽  
J. D. Henstridge
Keyword(s):  
Luteinizing Hormone ◽  
Breeding Season ◽  
Negative Feedback ◽  
Combined Treatment ◽  
Pulse Frequency ◽  
The Other ◽  
Ovarian Steroids ◽  
Pulsatile Secretion ◽  
Lh Secretion

The effects of oestradiol-17β, androstenedione, progesterone and time of the year on the pulsatile secretion of LH were tested in ovariectomized Merino ewes (n = 32). The steroids were administered by small subcutaneous implants, and the LH pulses were observed in samples taken at intervals of 15 min for 12 h in spring 1979, autumn 1980 and spring 1980, seasons corresponding to successive periods of anoestrus, breeding season and anoestrus. During spring, oestradiol alone was able to reduce the frequency of the LH pulses, while progesterone, either alone or in combination with oestradiol, had little effect. During autumn, on the other hand, neither oestradiol nor progesterone could significantly reduce the frequency of the pulses when administered independently, whereas the combined treatment was very effective. Androstenedione had no significant effect on pulse frequency at either time of the year, either alone or in any combination with oestradiol and progesterone. The basal levels of LH, over which the pulses are superimposed, were reduced by oestradiol alone in both seasons. Progesterone alone had no consistent effects, but interacted significantly with oestradiol and this combined treatment maintained low basal levels most effectively at all times. Androstenedione had no significant effect. The amplitude of the pulses increased throughout the course of the experiment. Within seasons, the amplitudes were significantly higher in the presence of oestradiol and progesterone, but were not significantly affected by androstenedione. It was concluded that certain of the ovarian steroids exert negative feedback on the tonic secretion of LH primarily by reducing the frequency of the pulses, and that the changes in LH secretion attributable to season and phases of the oestrous cycle can be accounted for entirely by the responses of the hypothalamus to oestradiol and progesterone. The role of the androstenedione secreted by the ovary in the ewe remains obscure.

The role of neuropeptide Y (NPY) in the control of LH secretion in the ewe with respect to season, NPY receptor subtype and the site of action in the hypothalamus

1995 ◽  
Vol 147 (3) ◽  
pp. 565-579 ◽  
Author(s):  
M L Barker-Gibb ◽  
C J Scott ◽  
J H Boublik ◽  
I J Clarke
Keyword(s):  
Neuropeptide Y ◽  
Breeding Season ◽  
Preoptic Area ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Suppressive Effect ◽  
Plasma Prolactin ◽  
Post Injection ◽  
Lh Secretion ◽  
Saline Vehicle

Abstract Neuropeptide Y1–36 (NPY1–36) acts through Y1 and Y2 receptors while the C-terminal NPY fragments NPY18–36 and N-acetyl[Leu28,31]pNPY24–36 act only through the Y2 receptor. We have investigated the effects of intracerebroventricular (i.c.v.) administration of NPY1–36, NPY18–36 and N-acetyl[leu28,31]pNPY24–36 on LH secretion in the ovariectomised (OVX) ewe. These peptides were administered into a lateral ventricle (LV) or the third ventricle (3V) of OVX ewes during the non-breeding and breeding seasons. Microinjections of NPY were also made into the preoptic area (POA) during both seasons to investigate the effects of NPY at the level of the GnRH cell bodies. Tamed sheep were fitted with 19 gauge guide tubes into the LV, 3V or the septo-preoptic area (POA). Jugular venous blood samples were taken every 10 min for 3 h. Sheep were then given NPY1–36 (10 μg), NPY18–36 (100 μg) or saline vehicle into the LV; N-acetyl[Leu28,31]pNPY24–36 (100 μg), NPY1–36 (10 μg or 100 μg), NPY18–36 (10 μg or 100 μg) or saline vehicle into the 3V, or NPY1–36 (1 μg, 5 μg, 10 μg) into the POA. Blood sampling continued for a further 3 h. LH was measured in plasma by radioimmunoassay. LV or 3V injection of 10 μg NPY1–36 caused a small but significant (P<0·025) increase in the interval from the last pre-injection pulse of LH to the first post-injection LH pulse during the breeding season. Other LH pulse parameters were not significantly affected. NPY18–36 did not produce any significant change in LH pulsatility when injected into the LV, and neither peptide had any effect on plasma prolactin or GH levels. There was a significant (P<0·01) reduction in LH pulse frequency after 3V injection of 10 μg and 100 μg NPY and 100 μg NPY18–36. Pulse amplitude was reduced by 3V administration of the Y2 agonist, N-acetyl[Leu28–31]pNPY24–36 and 100 μ NPY18–36. When the amplitude of the first post-injection LH pulse was analysed, 10 μg NPY also had a significant (P<0·05) suppressive effect. During the non-breeding season, 100 μg NPY1–36 (but not 10 μg) decreased (P<0·01) LH pulse frequency. LH pulse amplitude was significantly (P<0·01) decreased by 100 μg NPY18–36. Doses of 10 μg NPY1–36 and 100 μg NPY18–36 had greater inhibitory effects on pulse frequency during the breeding season but the suppressive effect of 100 μg NPY was similar between seasons. Microinjections of NPY into the POA decreased (P<0·01) average plasma LH levels during the non-breeding season at a dose of 10 μg but did not significantly affect pulse frequency or amplitude. We conclude that a substantial component of the inhibitory action of NPY on LH secretion in the absence of steroids is mediated by the Y2 receptor. This inhibition is probably exerted by way of a presynaptic action on GnRH terminals in the median eminence as NPY does not modulate the frequency or amplitude of LH pulses at the level of the GnRH cell bodies in the POA. Journal of Endocrinology (1995) 147, 565–579

scholarly journals Blunted Day-Night Changes in Luteinizing Hormone Pulse Frequency in Girls With Obesity: the Potential Role of Hyperandrogenemia

2014 ◽  
Vol 99 (8) ◽  
pp. 2887-2896 ◽  
Author(s):  
Jessicah S. Collins ◽  
Jennifer P. Beller ◽  
Christine Burt Solorzano ◽  
James T. Patrie ◽  
R. Jeffrey Chang ◽  
...  
Keyword(s):  
Potential Role ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Cross Sectional ◽  
Obese Adolescent ◽  
Clinical Research Center ◽  
Obese Subjects ◽  
Sectional Analysis ◽  
Lh Secretion

Context: Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown. Objective: The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia. Design: This was a cross-sectional analysis. Setting: The study was conducted at a clinical research center. Patients or Other Participants: Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study. Intervention: Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am. Main Outcome Measure: Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep). Results: Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively). Conclusions: Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.

Effects of bovine follicular fluid on the secretion of LH and FSH in inhibin-immunized seasonally anoestrous ewes

1991 ◽  
Vol 128 (3) ◽  
pp. 403-410 ◽  
Author(s):  
P. G. Knight ◽  
J. H. M. Wrathall ◽  
R. G. Glencross ◽  
B. J. McLeod
Keyword(s):  
Follicular Fluid ◽  
Synthetic Peptide ◽  
Pulse Frequency ◽  
Α Subunit ◽  
Blood Samples ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
And Control ◽  
Lh Secretion ◽  
Dose Dependent

ABSTRACT It has been shown previously that treatment of seasonally anoestrous ewes with steroid-free bovine follicular fluid (FF), a crude inhibin-containing preparation, leads to a decrease in plasma FSH level which is accompanied by a marked increase in pulsatile LH secretion. Since FF contains several factors (e.g. activin, follistatin, unidentified components) other than inhibin, which might act to modify gonadotrophin secretion, it was of interest to establish whether these concurrent effects of FF on FSH and LH secretion persisted in ewes which had been actively immunized against a synthetic peptide replica of the α subunit of bovine inhibin. In June 1989 (anoestrous period) groups of inhibin-immune and control ewes (n = 5 per group) received 6-hourly s.c. injections of either bovine serum (2 ml) or one of two doses of FF (0·5 ml or 2 ml) for 3 days. Blood was withdrawn at 6-h intervals for 6 days beginning 24 h before the first injection. On the final day of treatment, additional blood samples were withdrawn at 15-min intervals for 8 h to monitor pulsatile LH secretion. Ewes were then challenged with exogenous gonadotrophin-releasing hormone (GnRH; 2 μg i.v. bolus) to assess pituitary responsiveness. In control ewes, FF promoted a dose-dependent suppression of basal (maximum suppression 65%; P < 0·01) and post-GnRH (maximum suppression 72%; P < 0·01) levels of FSH in plasma. This was accompanied by an increase (P < 0·01) in LH pulse frequency from 1·40±0·24 (s.e.m.) to 3·20±0·37 pulses/8 h. In contrast, FF did not affect secretion of either FSH or LH in inhibin-immunized ewes. However, mean plasma LH levels in immunized ewes were significantly lower (43%; P < 0·02) than in control ewes, irrespective of treatment. These findings indicate that in the anoestrous ewe the ability of FF to suppress plasma FSH is due entirely to its content of inhibin, that FF-induced enhancement of pulsatile LH secretion is mediated by inhibin, rather than some additional component of FF, and that immunoneutralization of endogenous inhibin can reduce LH secretion. Journal of Endocrinology (1991) 128, 403–410

scholarly journals Glucagon-like peptide-1 control of GnRH secretion in female sheep

2021 ◽  
Author(s):  
Leila Arbabi ◽  
Qun Li ◽  
Belinda A Henry ◽  
Iain J Clarke
Keyword(s):  
Venous Blood ◽  
In Situ Hybridisation ◽  
Gnrh Secretion ◽  
Surrogate Measure ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Lh Secretion ◽  
Female Sheep

The role of glucagon-like peptide-1 (GLP-1) on gonadotropin releasing hormone (GnRH) secretion was investigated in ovariectomised (OVX) ewes, in which GnRH and luteinising hormone (LH) secretion had been restrained by treatment with estrogen and progesterone. Guide tubes for microinjection were placed above the ME and the animals allowed to recover for 1 month. Jugular venous blood samples were taken via cannulae at 10 min intervals. Vehicle (50nl) was injected into the ME at 2h, followed by injection of GLP-1 ((7-36)-amide - 0.5 or 1 nmole) or its receptor agonist, exendin 4 (0.5 nmole) at 4h (n=5). Plasma LH levels were quantified as a surrogate measure of GnRH secretion. GLP-1 microinjection into the ME elicited a large amplitude LH pulse in jugular plasma, the effect was greater at the higher dose. Exendin-4 microinjection caused a large, sustained increase in plasma LH levels. To determine how GLP-1 might exert an effect on GnRH secretion, we employed double labelled in situ hybridisation, with RNAScope, for co-localisation of the GLP-1 receptor (GLP-1R) in GnRH, Kisspeptin and NPY cells in the hypothalami of 3 ewes in the luteal phase of the estrous cycle. GLP-1R expression was clearly visible but the receptor was not expressed in GNRH1 or NPY expressing neurons and was visualised in <5% of KISS1 expressing neurons. We conclude that GLP-1 may act at the level of the secretory terminals of GnRH neurons in the ME to stimulate GnRH secretion, the pathway through which such effect is manifest remains unknown.

Patterns of spontaneous LH release in normo- and hyperprolactinaemic women

1981 ◽  
Vol 97 (3) ◽  
pp. 305-310 ◽  
Author(s):  
Maire T. Buckman ◽  
Glenn T. Peake ◽  
Laxima Srivastava ◽  
Josephine Morris ◽  
Barry David ◽  
...  
Keyword(s):  
Sampling Period ◽  
Normal Subjects ◽  
Plasma Prolactin ◽  
Early Follicular Phase ◽  
Lh Release ◽  
Normal Women ◽  
17 Hydroxyprogesterone ◽  
Group Sex ◽  
Lh Secretion

Abstract. Hyperprolactinaemia may be associated with functional amenorrhoea. In order to evaluate the possible role of abnormal spontaneous LH secretion in hyperprolactinaemic amenorrhoeic women, plasma LH was measured at 15 min intervals for 300 min in 12 normal women during the early follicular phase of the menstrual cycle and compared to that observed in 11 hyperprolactinaemic amenorrhoeic subjects. Mean plasma prolactin was 9.1 ± 3.6 ng/ml (x̄ ± sem) in the euprolactinaemic and 168 ± 32 ng/ml in the hyperprolactinaemic group. Sex steroids including oestrone, oestradiol, progesterone and 17-hydroxyprogesterone were similar in the 2 groups. Mean plasma LH levels over the 300 min sampling period were 9.4 ± 1.6 mIU/ml in the normal subjects and 7.5 ± 1.0 mIU/ml in the hyperprolactinaemic patients (P>0.10). Every normal woman exhibited at least one LH spike in excess of 10 mIU/ml. Five hyperprolactinaemic patients failed to exhibit any LH spikes above 10 mIU/ml (P < 0.02 compared to controls). Thus, hyperprolactinaemia was associated with an absence of LH spike activity in 45% of patients studied and this abnormality may play an aetiologic role in the hypogonadism observed in these subjects; in those hyperprolactinaemic subjects with pulsatile LH secretion, however, other explanations for their amenorrhoea should be considered.

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