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

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.

1995 ◽  
Vol 147 (2) ◽  
pp. 321-329 ◽  
Author(s):  
D W Miller ◽  
D Blache ◽  
G B Martin

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


1996 ◽  
Vol 8 (5) ◽  
pp. 855 ◽  
Author(s):  
S Tjondronegoro ◽  
GB Martin ◽  
SR Sutherland ◽  
R Boukhliq

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.


1999 ◽  
Vol 276 (1) ◽  
pp. H63-H70 ◽  
Author(s):  
Shereeni J. Veerasingham ◽  
Frans H. H. Leenen

To examine the role of the ventral anteroventral third ventricle (vAV3V) in the hypertension induced by chronic subcutaneous ouabain and intracerebroventricular hypertonic saline, neurons in this area were destroyed by microinjection of an excitotoxin, ibotenic acid. Sham-operated or lesioned Wistar rats were administered ouabain (50 μg/day) or placebo for 3 wk from subcutaneously implanted controlled release pellets or artificial cerebrospinal fluid (CSF) or CSF containing 0.8 mol/l NaCl (5 μl/h) infused intracerebroventricularly for 2 wk. At the end of the experiment, mean arterial pressure (MAP) and heart rate at rest and in response to ganglionic blockade by intravenous hexamethonium (30 mg/kg) were assessed. In rats infused with hypertonic saline, responses to air jet stress were also assessed. Baseline MAP in sham-operated rats receiving intracerebroventricular hypertonic saline or subcutaneous ouabain was significantly higher than in control rats (115 ± 1 vs. 97 ± 3 and 121 ± 3 vs. 103 ± 3 mmHg, respectively). vAV3V lesions abolished the increase in MAP elicited by chronic infusion of hypertonic saline or administration of ouabain. Sham-operated rats treated with hypertonic saline or ouabain exhibited significantly enhanced decreases in MAP to hexamethonium, but lesioned rats did not. Rats infused with hypertonic saline demonstrated enhanced responses to air jet stress that were similar in sham-operated and lesioned rats. These results demonstrate that neurons in the vAV3V are essential for the hypertension induced by intracerebroventricular hypertonic saline and subcutaneous ouabain, possibly by increasing sympathetic tone. Cardiovascular responses to air jet stress appear not to be mediated by the vAV3V.


2018 ◽  
Vol 16 (2) ◽  
pp. E51-E51
Author(s):  
Giorgio Palandri ◽  
Thomas Sorenson ◽  
Mino Zucchelli ◽  
Nicola Acciarri ◽  
Paolo Mantovani ◽  
...  

Abstract Cavernous malformations of the third ventricle are uncommon vascular lesions. Evidence suggests that cavernous malformations in this location might have a more aggressive natural history due to their risk of intraventricular hemorrhage and hydrocephalus.1 The gold standard of treatment is considered to be microsurgical gross total resection of the lesion. However, with progressive improvement in endoscopic capabilities, several authors have recently advocated for the role of minimally-invasive neuroendoscopy for resecting intraventricular cavernous malformations.2-4 In this timely intraoperative video, we demonstrate the gross total resection of a third ventricle cavernous malformation that presented with hemorrhage via a right-sided trans-frontal neuroendoscopic approach.


2008 ◽  
Vol 62 (suppl_1) ◽  
pp. ONS51-ONS56 ◽  
Author(s):  
Jeremy D.W. Greenlee ◽  
Charles Teo ◽  
Ali Ghahreman ◽  
Bernard Kwok

Abstract Objective: To further assess the safety and long-term efficacy of endoscopic resection of colloid cysts of the third ventricle. Methods: A retrospective review of a series of 35 consecutive patients (18 male, 17 female) with colloid cysts treated by endoscopic surgery was undertaken. Results: The mean patient age was 32.4 years (range, 11–54 yr). Headache was the most common presenting symptom (22 patients). The average tumor size was 18 mm (range, 3–50 mm). The endoscopic technique could not be completed in six patients, necessitating conversion to an open craniotomy and a transcortical approach to the colloid cyst. All patients had histologically confirmed colloid cysts of the third ventricle, and complete resection of the lesion was confirmed macroscopically and radiologically in all patients. There were no deaths. Two patients developed aseptic meningitis without any permanent sequelae. One patient developed unilateral hydrocephalus attributable to obstruction of the foramen of Monro, which was treated with endoscopic septum pellucidotomy. The median follow-up period was 88 months (range, 10–132 mo). There was one asymptomatic radiological recurrence. No seizures occurred after surgery. Conclusion: The results of this study support the role of endoscopic resection in the treatment of patients with colloid cysts as a safe and effective modality. In some cases, conversion to an open procedure may be required. Additional follow-up will be required to continue to address the duration of lesion-free survival.


1980 ◽  
Vol 95 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Martha Medina ◽  
Alfredo Ulloa-Aguirre ◽  
Maria A. Fernández ◽  
Gregorio Pérez-palacios

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.


2020 ◽  
Vol 35 (6) ◽  
pp. 1421-1431
Author(s):  
Karolina Skorupskaite ◽  
Jyothis T George ◽  
Johannes D Veldhuis ◽  
Robert P Millar ◽  
Richard A Anderson

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.


1983 ◽  
Vol 96 (2) ◽  
pp. 181-193 ◽  
Author(s):  
G. B. Martin ◽  
R. J. Scaramuzzi ◽  
J. D. Henstridge

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.


1989 ◽  
Vol 256 (3) ◽  
pp. R674-R684 ◽  
Author(s):  
E. Arnauld ◽  
V. Bibene ◽  
J. Meynard ◽  
F. Rodriguez ◽  
J. D. Vincent

The effect of arginine vasopressin (AVP) on the duration and the relative proportion of sleeping and wakeful periods has been investigated. Vigilance states were determined by visual scoring of polygraphic recordings from unrestrained rats. Animals were implanted with a cannula into the third ventricle through which AVP or related drugs, dissolved in artificial cerebrospinal fluid, were infused at a constant rate by an osmotic pump. Polygraphic data were collected 24 h/day from day 4 to day 9. Recordings were continued for 3 additional days during AVP recovery. AVP infusions significantly increased the amount of time spent in waking compared with control or recovery periods (12%). This effect was mimicked by an AVP agonist (2-phenylalanine, 8-ornithine oxytocin). Oxytocin, a peptide structurally close to AVP, induced a mild change in waking time. The infusion of an AVP antagonist, 1-desaminopenicillamine-2-(O-methyl)tyrosine-arginine vasopressin (dPTyr(Me)AVP), or of anti-AVP antibodies significantly decreased duration of waking. The infusion of antioxytocin antibodies did not modify the duration of waking. The effects of structural analogues of AVP relatively specific for each type of peripheral AVP receptor indicated the participation of a V1-like AVP receptor in the action of AVP on waking time. During infusion of anti-AVP antibodies and dPTyr(Me)AVP and during the first days of recovery from AVP infusion, the ultradian rhythmic distribution of sleep and wakefulness was still present, but the amplitude of the circadian rhythm was reduced.


2014 ◽  
Vol 99 (8) ◽  
pp. 2887-2896 ◽  
Author(s):  
Jessicah S. Collins ◽  
Jennifer P. Beller ◽  
Christine Burt Solorzano ◽  
James T. Patrie ◽  
R. Jeffrey Chang ◽  
...  

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.


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