Progesterone acutely increases LH pulse amplitude but does not acutely influence nocturnal LH pulse frequency slowing during the late follicular phase in women

2007 ◽  
Vol 292 (3) ◽  
pp. E900-E906 ◽  
Author(s):  
Christopher R. McCartney ◽  
Susan K. Blank ◽  
John C. Marshall

Progesterone (P) is the primary effector of LH (and by inference gonadotropin-releasing hormone) pulse frequency slowing in cycling women, but the time course of this action is unclear. We hypothesized that P administration to estradiol (E2)-pretreated women would slow LH pulse frequency within 12 h. We studied eight normally cycling women in two separate cycles (follicular phase, cycle days 7–11). After 3 days of E2 pretreatment (0.2 mg/day via transdermal patches), a 25-h blood sampling protocol (starting at 0800) was performed to define LH pulsatility. Oral micronized P (100 mg) or placebo (PBO) was administered at 1800 in a randomized, double-blind fashion, with treatment crossover occurring during a subsequent cycle. The 10-h mean P concentration increased from 0.6 ± 0.1 ng/ml before P (0800–1800) to 3.9 ± 0.3 ng/ml after P administration (2200–0800, P < 0.01). Ten-hour mean LH interpulse interval increased significantly after both P and PBO administration, with no significant difference between P and PBO. In contrast, mean LH, LH amplitude, and mean FSH increased significantly within 4 h of P administration, but not after PBO. We conclude that, in E2-pretreated women in the late follicular phase, 1) nocturnal LH pulse frequency is not acutely (within 12 h) influenced by P administration; 2) an acute increase in P causes pronounced augmentation of gonadotropin pulse amplitude within 4 h; and 3) LH pulse frequency slows overnight during the second half of the follicular phase.

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


Author(s):  
Aty Widyawaruyanti ◽  
Arijanto Jonosewojo ◽  
Hilkatul Ilmi ◽  
Lidya Tumewu ◽  
Ario Imandiri ◽  
...  

Abstract Objectives Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers. Methods The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated. Results There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet Conclusions The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic.


1989 ◽  
Vol 120 (3) ◽  
pp. 497-502 ◽  
Author(s):  
S. M. Rhind ◽  
S. McMillen ◽  
W. A. C. McKelvey ◽  
F. F. Rodriguez-Herrejon ◽  
A. S. McNeilly

ABSTRACT The effects of body fat content (body condition) of ewes on hypothalamic activity and gonadotrophin-releasing hormone (GnRH) secretion and on pituitary sensitivity to GnRH were investigated using Scottish Blackface ewes. Two groups of 12 ewes were fed so that they achieved either a high body condition score (2·98, s.e.m. = 0·046; approximately 27% of empty body weight as fat) or a low body condition score (1·94, s.e.m. = 0·031; approximately 19% of empty body weight as fat) by 4 weeks before the period of study. Thereafter, they were differentially fed so that the difference in mean condition score was maintained. Oestrus was synchronized, and on day 11 of the subsequent cycle half of the ewes of each group were ovariectomized. On day 12, the remaining ewes were injected (i.m.) with 100 μg prostaglandin F2α analogue and ovariectomized 30 h later. Numbers of large ovarian follicles and corpora lutea present at ovariectomy were recorded. Blood samples were collected at 15-min intervals for 12 h on day 10 of the cycle (luteal phase) and at 10-min intervals from 24 to 30 h after prostaglandin injection (follicular phase). At days 2 and 7 after ovariectomy, samples were collected at 15-min intervals for 8 h and ewes were then injected with 10 μg GnRH and samples were collected for a further 3 h. Samples were assayed for LH and FSH. Ewes in high body condition had more more large follicles than ewes in low body condition during the luteal phase (15·3 vs 6·5; P < 0·05) and follicular phase (11·5 vs 7·0; NS) and a slightly higher mean ovulation rate (1·50 vs 1·20; NS). However, during the luteal and follicular phases of the cycle before ovariectomy there was no effect of condition score on mean LH or FSH concentrations or mean LH pulse frequency or pulse amplitude. Two days after ovariectomy, ewes of high body condition had a higher mean LH pulse frequency than ewes of low body condition (P < 0·05) and higher mean FSH concentrations (P < 0·05). Mean LH concentration and pulse amplitude were not affected. LH and FSH profiles were not affected by body condition on day 7. GnRH-induced increases in LH and FSH concentrations on days 2 and 7 were not affected by body condition. At day 7, but not day 2, ewes ovariectomized during the luteal phase of the cycle had a significantly (P < 0·05) greater GnRH-induced LH release compared with ewes ovariectomized during the follicular phase. It is concluded that body condition directly affects hypothalamic activity and GnRH secretion, but not pituitary sensitivity to GnRH, and that effects on reproductive performance are also mediated through changes in ovarian hormones or in hypothalamo-pituitary sensitivity to ovarian hormones. Journal of Endocrinology (1989) 120, 497–502


1989 ◽  
Vol 49 (2) ◽  
pp. 267-273 ◽  
Author(s):  
S. M. Rhind ◽  
S. McMillen ◽  
G. Z. Wetherill ◽  
W. A. C. McKelvey ◽  
R. G. Gunn

ABSTRACTGonadotrophin profiles during the follicular phase of the cycle prior to a synchronized mating and LH and progesterone profiles at days 2, 6 and 10 post mating were investigated in three groups of 16 ewes. of one group were given 0·5 × estimated metabolizable energy requirements for maintenance (MEM) from 14 days before mating until slaughter 11 days after mating (LL). Ewes of a second group were given 1·5 × MEM during the 14 days prior to mating and then 0·5 × MEM thereafter (HL) and the remaining ewes (HH) were given 1·5 × maintenance throughout the experiment. During the day before mating, plasma samples were collected at 10-min intervals for 8 h and assayed for LH and FSH. Samples were collected at 15-min intervals for 8 h on days 2, 6 and 10 after mating. Each ewe was then injected intravenously with 10 μg LH and samples were collected for a further 3 h. All of these samples were assayed for LH and progesterone. Nutritional treatment did not affect mean follicular phase concentrations of FSH or LH or mean LH pulse amplitude but the mean LH pulse frequency (pulses per h) of LL ewes was lower than that of HH + HL ewes (0·37 v. 0·48; P < 0·05). After mating, mean LH concentrations were unaffected by sampling date or nutritional treatment but the mean LH pulse frequency was lower in HL + LL than HH ewes at day 2 (0·25 v. 0·40; P < 0·01) and day 10 (0·28 v. 0·38; P < 0·05). Mean progesterone concentrations (ng/1) were higher in HL + LL than HH ewes at day 10 (6·77 v. 4·80; P < 0·05) but pulse frequency was not significantly affected. Injection of 10 μg LH on days 2, 6 and 10 after mating was followed by a significant increase in progesterone concentrations. The progesterone response was greater (P < 0·05) in LL + HL ewes than in HH ewes. It is concluded that increased rates of embryo mortality often associated with undernutrition are unlikely to be related to lower circulating progesterone levels per se but may be attributable to reductions in mean LH pulse frequency and consequent changes in progesterone profiles.


1985 ◽  
Vol 107 (3) ◽  
pp. 429-436 ◽  
Author(s):  
G. Shaw ◽  
G. I. Jorgensen ◽  
R. Tweedale ◽  
M. Tennison ◽  
M. J. Waters

ABSTRACT Adult Merino ewes were infused via the jugular vein with either saline (n = 5) or epidermal growth factor (EGF) (4·2 μg/kg per h, n = 6) for 24 h in either the luteal phase or the follicular phase of the oestrous cycle and reproductive function was examined. Infusion of EGF during the luteal phase caused no detectable change in plasma progesterone or prolactin concentrations over a 7-day period compared with the controls. Infusion of EGF during the follicular phase suppressed the oestrous rise in plasma oestradiol. Luteinizing hormone pulse amplitude was increased and pulse frequency was decreased by the end of the infusion. All control ewes had a pro-oestrous LH surge and mated, but the LH surge and oestrus were prevented by EGF infusion. Nevertheless, plasma progesterone levels rose subsequently in the EGF-infused ewes in parallel with the control ewes, suggesting that the preovulatory follicle had luteinized. Both LH and FSH rose over the 7 days after EGF infusion to levels similar to those in ovariectomized ewes. Thus EGF appears to inhibit follicular oestradiol production, although it does not affect luteal progesterone production or follicular luteinization. We suggest that the alteration in gonadotrophin secretion patterns results from a disturbance of feedback mechanisms between the ovary and the hypothalamopituitary axis, although a direct effect in the brain or the pituitary gland cannot yet be excluded. J. Endocr. (1985) 107, 429–436


2018 ◽  
Vol 5 (10) ◽  
Author(s):  
Sharon A Riddler ◽  
Lu Zheng ◽  
Christine M Durand ◽  
Justin Ritz ◽  
Richard A Koup ◽  
...  

Abstract Background Broadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals. Methods A5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9. Results Infusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms (P = .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4+ T cells between arms (both P &gt; .05). Conclusions In individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4+ T cells. ClinicalTrials.gov Identifier NCT02411539


1999 ◽  
pp. 257-266 ◽  
Author(s):  
T Mulligan ◽  
A Iranmanesh ◽  
R Kerzner ◽  
LW Demers ◽  
JD Veldhuis

OBJECTIVE: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency. DESIGN: We used a randomized, double-blind, placebo-controlled design. METHODS: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.v. every 90 min). RESULTS: At baseline (saline infusion), older men had more LH pulses (young compared with old, 10 +/- 0.6 compared with 15 +/- 1, P = 0.0026) per 24h, reduced fractional LH pulse amplitude (219 +/- 17% compared with 167 +/- 40%, P = 0.0376), and more disorderly hormone release as judged by approximate entropy (ApEn) (LH, P < or = 0.0001; testosterone, P < or = 0.0047). In response to pulsatile i.v. GnRH infusions, serum 24-h LH concentrations (measured by immunoradiometric assay (IRMA)), increased equivalently in young and older men (to 7.3 +/- 1.2 and 7.2 +/- 1.8 IU/l respectively). GnRH treatment also normalized LH pulse frequency and amplitude, ApEn, and plasma biologically active LH (pooled) concentrations. In contrast, 24-h testosterone concentrations failed to increase equivalently in older men (young compared with old, 869 +/- 88 compared with 517 +/- 38 ng/dl, P = 0.0061), reflecting lower testosterone peak maxima (995 +/- 108 compared with 583 +/- 48 ng/dl, P = 0.0083) and interpeak nadirs (750 +/- 87 compared with 427 +/- 26 ng/dl, P = 0.0073). CONCLUSIONS: We have demonstrated that, in older men, successful reconstitution of 24-h pituitary (bioactive) LH output and pulsatile (IRMA) LH release patterns could be achieved by a fixed exogenous GnRH pulse signal, thereby implicating altered endogenous hypothalamic GnRH release in the relative hypogonadotropism of aging. The failure of testosterone concentrations to increase concomitantly points to a simultaneous Leydig cell defect. We conclude that aging in men is marked by a dual defect in the central nervous system-pituitary-Leydig cell axis.


2014 ◽  
Vol 306 (11) ◽  
pp. E1292-E1304 ◽  
Author(s):  
W. K. McGee ◽  
C. V. Bishop ◽  
C. R. Pohl ◽  
R. J. Chang ◽  
J. C. Marshall ◽  
...  

Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants ( n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15–19% (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that of T-treated animals, whereas LH pulse amplitude decreased in both groups and remained low. The numbers of antral follicles present during the early follicular phase increased in both groups on the WSD, but maximal follicular size decreased by 50%. During the late follicular phase, T-treated females had greater numbers of small antral follicles than controls. T-treated monkeys also had lower progesterone during the luteal phase of the menstrual cycle. Although fasting insulin did not vary between groups, T-treated animals had decreased insulin sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some features characteristic of PCOS, T + WSD caused a more severe phenotype with regard to insulin insensitivity, increased numbers of antral follicles at midcycle, and decreased circulating luteal phase progesterone levels.


2001 ◽  
Vol 280 (2) ◽  
pp. H628-H633 ◽  
Author(s):  
Pierre Boutouyrie ◽  
Robert Corvisier ◽  
Michel Azizi ◽  
Dominique Lemoine ◽  
Brigitte Laloux ◽  
...  

Palpation of the radial pulses is an important technique in traditional Chinese medicine. Two double-blind randomized trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitized subjects) and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform were measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-min acupuncture period. In sensitized patients, arterial diameter significantly increased during real acupuncture, compared with the sham group (+7.5 ± 2.8 vs. −2.9 ± 2.7%, respectively; P < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time course of blood pressure, radial artery distensibility, and pressure waveform. Our results demonstrate that real acupuncture is associated with an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.


Author(s):  
S. R. Gayathri ◽  
Saswati Tripathy ◽  
M. Muthulakshmi

Background: Hypothalamic pituitary axis dysfunction accounts for majority of ovulatory disorders and a predominant cause of women with PCOS. There is a dopaminergic control on gonadotropin secretion. In normoprolactinemic PCOS patients transient rise in serum prolactin can be observed during the late follicular phase and luteal phase. So, the aim of the study is to know the effect of bromocriptine and clomiphene in ovulation induction as compared to clomiphene alone.Methods: Based on the various inclusion and exclusion criteria, seventy patients were randomly assigned into two groups. The patients in the first group were treated with tablet of clomiphene citrate (100 mg) from day 3 to day 7 of each cycle. The patients in the other group received 100mg of clomiphene citrate from day 3 to day 7 of each cycle and tablet bromocriptine (2.5 mg) from day5 to day14. Both groups were followed up with follicular study for three months. At the end of the three cycles the hormonal statuses of the patients were determined.Results: There was no significant difference found in other hormones like serum FSH, LH and estradiol in both groups. The follicular diameter and the average endometrial thickness was increased to a significant level in the CC+Bcrt group as compared to the CC group. The rate of ovulation and pregnancy rate was higher in combination group.Conclusions: Bromocriptine with clomiphene in follicular phase has an advantage of improving follicular diameter, endometrial thickness and hence ovulation and pregnancy rates. 


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