LH pulsatility and in vitro bioactivity in women with anorexia nervosa-related hypothalamic amenorrhea

1991 ◽  
Vol 125 (6) ◽  
pp. 614-620 ◽  
Author(s):  
Jacques Allouche ◽  
Antoine Bennet ◽  
Pierre Barbe ◽  
Monique Plantavid ◽  
Philippe Caron ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
In Vitro Bioactivity ◽  
Hypothalamic Amenorrhea ◽  
Blood Samples ◽  
Lh Pulsatility ◽  
Normal Women

Abstract. LH nocturnal pulsatility and bioactivity to immunoreactivity (B/I) ratio were determined in 16 patients with anorexia nervosa-related hypothalamic amenorrhea and low sex steroid levels, and in 12 normal women in the midfollicular phase. The patients were subdivided into 2 groups: IA (N=7) without, and IB (N=9) with documented recent weight gain. Blood samples were taken from each subject at 10-min intervals from 00.00 to 06.00 h. Immunoreactive LH data were analysed with cluster analysis algorithm. A pool of aliquots from all the samples was used to evaluate bioactive LH, immunoreactive LH and LH B/I ratio in each subject. LH pulse frequency was lower in Group IA than in controls, whereas it did not differ significantly between Group IB and controls. LH pulse amplitude was lower in Group IA, and higher in Group IB than in controls. LH B/I ratio was below the control range in 3/16 patients. In conclusion, persistent hypothalamic amenorrhea does not require a permanent inhibition of the GnRH pulse generator; transient inhibition of pulsatility and qualitative abnormalities of gonadotropins could be involved in the mechanism, at least in some patients.

scholarly journals Development of Gonadotropin-Releasing Hormone-1 Secretion in Mouse Nasal Explants

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3221-3227 ◽  
Author(s):  
Stephanie Constantin ◽  
Alain Caraty ◽  
Susan Wray ◽  
Anne H. Duittoz
Keyword(s):  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Early Developmental Stage ◽  
Limiting Factor ◽  
Sequence Of Events ◽  
Natural Ligands ◽  
Early Developmental ◽  
Secretory Pattern

Pulsatile release of GnRH-1 is critical to stimulate gonadotropes of the anterior pituitary. This secretory pattern seems to be inherent to GnRH-1 neurons, however, the mechanisms underlying such episodical release remain unknown. In monkey nasal explants, the GnRH-1 population exhibits synchronized calcium events with the same periodicity as GnRH-1 release, suggesting a link, though the sequence of events was unclear. GnRH-1 neurons in mouse nasal explants also exhibit synchronized calcium events. In the present work, GnRH-1 release was assayed in mouse nasal explants using radioimmunology and its relationship with calcium signaling analyzed. GnRH-1 neurons generated episodical release as early as 3 d in vitro (div) and maintained such release throughout the period studied (3–21 div). The pulse frequency remained constant, suggesting that the pulse generator is operative at an early developmental stage. In contrast, pulse amplitude increased 2-fold between 3 and 7 div, and again between 7 and 14 div, suggesting maturation in synthesizing and/or secretory mechanisms. To evaluate these possibilities, total GnRH-1 content was measured. Only a small increase in GnRH-1 content was detected between 7 and 14 div, whereas a large increase occurred between 14 and 21 div. These data indicate that GnRH-1 content was not a limiting factor for the amplitude of the pulses at 7 div but that the secretory mechanisms mature between 3 and 14 div. The application of kisspeptin-10 revealed the ability of GnRH-1 neurons to integrate signals from natural ligands into a secretory response. Finally, simultaneous sampling of medium and calcium imaging recordings indicated that the synchronized calcium events and secretory events are congruent.

scholarly journals Pubertal Acceleration of Pulsatile Gonadotropin-Releasing Hormone Release in Male Rats as Revealed by Microdialysis

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Glenn C. Harris ◽  
Jon E. Levine
Keyword(s):  
Vas Deferens ◽  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Male Rats ◽  
Male Rat ◽  
Pubertal Maturation ◽  
Repeated Sampling ◽  
Generator Activity ◽  
Mature Spermatozoa

Abstract A microdialysis technique was used in male rats to directly assess the postulate that pubertal maturation is associated with accelerated GnRH pulsatility. Juvenile male rats, postnatal d 43 or 45 (n = 4) were stereotaxically fitted with guide cannulas directed toward the lateral median eminence, and repeated microdialysis experiments were conducted over 4–6 d. In each session, samples were collected continuously over 12 h (0900–2100 h) at 5-min intervals Results from individual peripubertal animals were pooled into two time bins for postnatal d 45–47 and 48–50, respectively, and GnRH characteristics were compared between the two epochs. The GnRH pulse frequency and mean GnRH concentration were significantly elevated at 48–50 d compared with 45–47 d. The GnRH pulsatility characteristics for 45–47 d vs. 48–50 d were as follows: pulse frequency, 0.74 ± 0.16 vs. 1.79 ± 0.19 pulses/h (P < 0.05); pulse amplitude, 254.1 ± 22.3 vs. 347.2 ± 15.8 Δpg/ml (difference in value from trough to peak); and mean release, 0.55 ± 0.03 vs. 2.04 ± 0.04 pg/5 min (P < 0.05). An additional two rats were dialyzed only once on postnatal d 50 to assess the effects of repeated sampling; the GnRH pulse characteristics in these animals were similar to those in rats sampled for a third or fourth time on postnatal d 48–50. To further assess the possible effects of repeated sampling on GnRH release profiles, a group of adult male rats (postnatal d 95–105; n = 3) was also dialyzed on four consecutive days. In these rats no significant alteration in GnRH pulse generator activity was observed over the four sessions. Moreover, the increase in GnRH pulse frequency observed in the peripubertal rats was found to be sustained in adult animals. To better understand the temporal relationship of GnRH pulse generator activity to reproductive maturation, groups of male rats were killed from postnatal d 45–56 along with an adult group at 95–105 d (n = 5/group) and examined for physiological signs of reproductive development. Gradual increases in serum levels of LH and testosterone and decreases in FSH and inhibin B were seen from postnatal d 45–56 to adulthood. Mature spermatozoa were found in the vas deferens by postnatal d 53. Our results demonstrate that in the late juvenile stage of male rat development, GnRH pulse generator activity is gradually accelerated over the course of consecutive days. This acceleration occurs over a period during which serum LH and testosterone are rising to adult levels, and it precedes the presence of mature spermatozoa in the vas deferens by 3 d. Our observations provide direct support for the hypothesis that an acceleration of GnRH pulsatility is the critical neural stimulus for the initiation of pubertal maturation in males. The peripheral and central cues that prompt the pubertal activation of the GnRH pulse generator remain to be characterized.

Pulsatile LH secretion in streptozotocin-induced diabetes in the rat

1991 ◽  
Vol 131 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Q. Dong ◽  
R. M. Lazarus ◽  
L. S. Wong ◽  
M. Vellios ◽  
D. J. Handelsman
Keyword(s):  
Weight Loss ◽  
Insulin Treatment ◽  
Pulse Generator ◽  
Latin Square ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Metabolic Effect ◽  
Male Rat ◽  
Free Access ◽  
Lh Secretion

ABSTRACT This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1–1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P=0·001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feed-back. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss. The impaired pituitary responsiveness to GnRH is at least partly involved in the reduction of LH pulse amplitude. Journal of Endocrinology (1991) 131, 49–55

scholarly journals INFLUENCE OF SEASON AND SOCIAL ENVIRONMENT ON THE REPRODUCTIVE-ENDOCRINE STATUS OF THE ADULT LANDRACE BOAR

1990 ◽  
Vol 70 (1) ◽  
pp. 121-128 ◽  
Author(s):  
V. L. TRUDEAU ◽  
L. M. SANFORD
Keyword(s):  
Social Environment ◽  
Late Summer ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Social Environments ◽  
Blood Samples ◽  
Testosterone Secretion ◽  
Endocrine Status ◽  
Reproductive Endocrine ◽  
Basal Concentration

Seasonal variations in LH, FSH, and testosterone secretion were investigated for adult Landrace boars housed in different social environments for 1 yr. Socially nonrestricted boars (n = 4) were penned adjacent to ovariectomized gilts that were hormonally brought into estrus every 2 wk, while socially restricted boars (n = 4) were kept in pens with solid walls. Mean hormone concentrations were determined from the assay of single AM and PM blood samples collected from the jugular vein by venipuncture once a month. In November, February, May and August, blood samples were collected serially over 12 h from jugular catheters for assessment of pulsatile LH and testosterone secretion, and the LH response to a GnRH injection (1 μg kg−1 body weight). Mean LH and testosterone concentrations were relatively high in all boars during the late summer and fall, and often were greater for the socially nonrestricted versus the restricted boars (group × month), P < 0.05) in the winter (December and January). Mean FSH concentration also varied with month (P < 0.05). Pulse analysis indicated that higher mean testosterone concentrations in November and August were the result of increases (month, P < 0.05) in testosterone-pulse frequency and basal concentration. Maximal mean LH concentration in August was associated with maximal (month, P < 0.05) LH-pulse amplitude and basal concentration. The amplitude of the LH peak following GnRH injection increased (P < 0.05) between November and May, and remained high in August. Key words: Gonadotropins, testosterone, blood, season, social environment, boar

Effects of light and food on plasma leptin concentrations in ewes

2000 ◽  
Vol 71 (2) ◽  
pp. 235-242 ◽  
Author(s):  
T. Tokuda ◽  
T. Matsui ◽  
H. Yano
Keyword(s):  
Diurnal Rhythm ◽  
Energy Requirement ◽  
Pulse Length ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Pulse Plasma ◽  
Dark Cycle ◽  
Blood Samples ◽  
The Mean ◽  
Plasma Leptin

AbstractPlasma leptin concentration shows pulsatility and diurnal rhythm in humans. However, there are few reports concerning the 24-h profile of circulating leptin levels in ruminants. Five crossbred ewes were housed in metabolism cages under a 1-h light-dark cycle. The ewes were offered alfalfa hay daily to meet their energy requirement. Blood samples were collected at 15-min intervals for 24 h. Plasma leptin concentrations were determined using a radioimmunoassay and the profile of plasma leptin levels was analysed by the PULSAR algorithmic program for detecting pulse. Plasma leptin concentration changed in a pulsatile fashion. The mean leptin concentration was 2·93 ng/ml. The mean pulse frequency was 4·8 pulses per day and the mean pulse amplitude was 0·67 ng/ml with an average pulse length of 1:13 h. Plasma leptin level was not affected by feeding or lighting cycle. These results indicate that plasma leptin level in sheep shows pulsatility but diurnal rhythm is not exhibited.

Generation of growth hormone pulsatility in women: evidence against somatostatin withdrawal as pulse initiator

2001 ◽  
Vol 280 (3) ◽  
pp. E489-E495 ◽  
Author(s):  
Eleni V. Dimaraki ◽  
Craig A. Jaffe ◽  
Roberta Demott-Friberg ◽  
Mary Russell-Aulet ◽  
Cyril Y. Bowers ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Growth Hormone ◽  
Postmenopausal Women ◽  
Normal Saline ◽  
Driving Force ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Blood Samples ◽  
Stable Plasma ◽  
Plasma Gh

To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 μg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 ± 3 yr, body mass index 24.7 ± 1.2 kg/m2) were studied during normal saline and octreotide infusion providing stable plasma octreotide levels of 2,567 ± 37 pg/ml. Blood samples were obtained every 10 min for 24 h, and plasma GH was measured with a sensitive chemiluminometric assay. Octreotide infusion suppressed 24-h mean GH by 84 ± 3% ( P = 0.00026), GH pulse amplitude by 90 ± 3% ( P = 0.00031), and trough GH by 54 ± 5% ( P = 0.0012), whereas GH pulse frequency remained unchanged. The response of GH to GH-releasing hormone (GHRH) was not suppressed, and the GH response to GH-releasing peptide-6 (GHRP-6) was unaffected. We conclude that, in women, periodic declines in hypothalamic SRIH secretion are not the driving force of endogenous GH pulses, which are most likely due to episodic release of GHRH and/or the endogenous GHRP-like ligand.

scholarly journals Androgen Suppresses In Vivo and In Vitro LH Pulse Secretion and Neural Kiss1 and Tac2 Gene Expression in Female Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Lourdes A Esparza ◽  
Tomohiro Terasaka ◽  
Mark A Lawson ◽  
Alexander S Kauffman
Keyword(s):  
Gene Expression ◽  
Pulse Frequency ◽  
Normal Male ◽  
Steroid Abuse ◽  
Female Mice ◽  
Reproductive Axis ◽  
Lh Pulsatility ◽  
Lh Secretion

Abstract Androgens can affect the reproductive axis of both sexes. In healthy women, as in men, elevated exogenous androgens decrease gonad function and lower gonadotropin levels; such circumstances occur with anabolic steroid abuse or in transgender men (genetic XX individuals) taking androgen supplements. The neuroendocrine mechanisms by which endogenous or exogenous androgens regulate gonadotropin release, including aspects of pulsatile luteinizing hormone (LH) secretion, remain unknown. Because animal models are valuable for interrogating neural and pituitary mechanisms, we studied effects of androgens in the normal male physiological range on in vivo LH secretion parameters in female mice and in vitro LH secretion patterns from isolated female pituitaries. We also assessed androgen effects on hypothalamic and gonadotrope gene expression in female mice, which may contribute to altered LH secretion profiles. We used a nonaromatizable androgen, dihydrotestosterone (DHT), to isolate effects occurring specifically via androgen receptor (AR) signaling. Compared with control females, DHT-treated females exhibited markedly reduced in vivo LH pulsatility, with decreases in pulse frequency, amplitude, peak, and basal LH levels. Correlating with reduced LH pulsatility, DHT-treated females also exhibited suppressed arcuate nucleus Kiss1 and Tac2 expression. Separate from these neural effects, we determined in vitro that the female pituitary is directly inhibited by AR signaling, resulting in lower basal LH levels and reduced LH secretory responses to gonadotropin-releasing hormone pulses, along with lower gonadotropin gene expression. Thus, in normal adult females, male levels of androgen acting via AR can strongly inhibit the reproductive axis at both the neural and pituitary levels.

scholarly journals Central Infusion of Agouti-Related Peptide Suppresses Pulsatile Luteinizing Hormone Release in the Ovariectomized Rhesus Monkey

Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 784-789 ◽  
Author(s):  
Nicolas R. Vulliémoz ◽  
Ennian Xiao ◽  
Linna Xia-Zhang ◽  
Sharon L. Wardlaw ◽  
Michel Ferin
Keyword(s):  
Pulse Generator ◽  
Third Ventricle ◽  
Reproductive Function ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Melanocortin Receptor ◽  
Central Administration ◽  
Related Peptide ◽  
Orexigenic Peptide ◽  
Lh Release

Abstract Agouti-related peptide (AGRP), an endogenous melanocortin receptor antagonist, is a powerful orexigenic peptide when infused centrally. AGRP and neuropeptide Y (NPY), another orexigenic peptide, are colocated within the same neurons in the arcuate nucleus. Both NPY and AGRP mRNA expression increases during food restriction, a condition that is known to suppress the GnRH pulse generator and reproductive function. Although NPY has been shown previously to suppress LH secretion in the ovariectomized monkey, data on AGRP are lacking. In this study, we examined the effect of AGRP infusion into the third ventricle on pulsatile LH release in five adult monkeys. The 8-h protocol included a 3-h intraventricular saline infusion to establish baseline pulsatile LH release, followed by a 5-h infusion of AGRP (83–132) [5 μg/h (n = 1) or 10 μg/h (n = 4)]. In separate experiments, each animal received an 8-h saline treatment as a control. Blood samples were collected every 15 min for LH measurements. Cortisol levels were measured every 45 min. AGRP infusion significantly decreased LH pulse frequency (from a baseline of 0.74 ± 0.07 pulse/h to 0.36 ± 0.12 during AGRP infusion; P &lt; 0.01) and mean LH concentrations (to 41.1 ± 7.5% of baseline by h 5 of AGRP infusion; P &lt; 0.001). LH pulse amplitude was not modified by AGRP treatment. AGRP infusion also significantly increased cortisol release, as previously reported. The data demonstrate that central administration of AGRP inhibits pulsatile LH release in the monkey and suggest that AGRP, like NPY, may mediate the effect of a negative energy balance on the reproductive system by suppressing the GnRH pulse generator.

3β-Hydroxysteroid dehydrogenase inhibitor reduces ovarian steroid production but increases ovulation rate in the ewe: interactions with gonadotrophins and inhibin

1992 ◽  
Vol 134 (1) ◽  
pp. 115-125 ◽  
Author(s):  
R. Webb ◽  
G. Baxter ◽  
D. McBride ◽  
A. S. McNeilly
Keyword(s):  
Detrimental Effect ◽  
Pulse Amplitude ◽  
Hydroxysteroid Dehydrogenase ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Lh Secretion ◽  
Higher Doses

ABSTRACT Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles >6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion. Journal of Endocrinology (1992) 134, 115–125

scholarly journals Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4993-5001 ◽  
Author(s):  
Chad D. Foradori ◽  
Marcel Amstalden ◽  
Lique M. Coolen ◽  
Sushma R. Singh ◽  
Christine J. McManus ◽  
...  
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Brain Regions ◽  
Orphanin Fq ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
External Zone ◽  
Gnrh Secretion

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg14, Lys15] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.

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