scholarly journals Evidence that Orphanin FQ Mediates Progesterone Negative Feedback in the Ewe

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4249-4258 ◽  
Author(s):  
Casey C Nestor ◽  
Lique M. Coolen ◽  
Gail L. Nesselrod ◽  
Miro Valent ◽  
John M. Connors ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Luteal Phase ◽  
Arcuate Nucleus ◽  
Pulse Amplitude ◽  
Estrogen Receptor Α ◽  
Pulse Frequency ◽  
Orphanin Fq ◽  
High Degree ◽  
Lh Secretion

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.

Evidence that the switch from negative to positive feedback at the level of the pituitary gland is an important timing event for the onset of the preovulatory surge in LH in the ewe

1995 ◽  
Vol 145 (2) ◽  
pp. 271-282 ◽  
Author(s):  
I J Clarke
Keyword(s):  
Pituitary Gland ◽  
Negative Feedback ◽  
Luteal Phase ◽  
Bolus Injection ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Lh Surge ◽  
Small Rise ◽  
Lh Secretion

Abstract Experiments were performed to test the hypothesis that there is a negative feedback 'clamp' of ovarian hormones on the hypothalamus and pituitary gland during the follicular phase of the oestrous cycle that limits the secretion of GnRH and LH. GnRH secretion was monitored by sampling the hypophysial portal blood of ewes during the luteal phase of the oestrous cycle and either 24 h or 48 h after the induction of luteolysis by the injection of cloprostenol, a prostaglandin analogue. There was an increase in GnRH pulse frequency in the transition from the luteal to the follicular phase of the cycle. A reduction in the amplitude of GnRH pulses did not occur until 48 h after cloprostenol, suggestive of negative feedback at the level of the hypothalamus that is more profound in the latter part of the follicular phase. The responsivity of the pituitary gland to GnRH was monitored in ewes during the luteal phase of the oestrous cycle and 24 h or 48 h after cloprostenol. Injections of 250 ng or 1000 ng GnRH were given (i.v.) to ewes that had been anaesthetised to suppress endogenous secretion of GnRH and LH. Using the lower dose, the responses 48 h after cloprostenol were not significantly different from those in the luteal phase. With the higher dose of GnRH, a significant (P<0·05) increase in mean responsivity was seen 48 h after cloprostenol. There was, however, a marked variation in response, with some ewes showing profound increases in LH secretion in response to GnRH and others showing responses that were similar to those obtained during the luteal phase of the cycle. These data are interpreted to mean that the secretion of LH is 'clamped' during the follicular phase of the oestrous cycle and the 'clamp' is only released near the time of the preovulatory LH surge. To test whether or not a rise in GnRH input to the pituitary gland could over-ride the 'clamp' on the pituitary secretion of LH in the late follicular phase of the cycle, sheep were treated 40 h after cloprostenol with either a bolus injection of 500 ng GnRH or four pulses of 125 ng GnRH given at 10-min intervals. These treatments caused small elevations in LH secretion but did not always cause preovulatory LH surges. In some cases, a small rise in LH secretion was induced by GnRH treatments and levels of LH in plasma returned to baseline with the preovulatory LH surge occurring a few hours later. In one clear case, a bolus injection of GnRH induced an LH surge. The overall data from the GnRH-treated groups, however, indicated a significant delay in the onset of the LH surge which may have been due to perturbation of the subcellular mechanisms in the gonadotrophs. These data were interpreted to mean that the secretion of LH from the pituitary gland is inhibited up to very soon before the onset of the LH surge. The inhibitory factor could be oestrogen but could also be some other pituitary feedback hormone such as gonadotrophin surge-attenuating factor. It is concluded that the increase in the secretion of GnRH at the time of the onset of the LH surge is closely linked to an increase in the responsivity of the gonadotrophs to GnRH. The latter is not caused by the increase in the secretion of GnRH. Journal of Endocrinology (1995) 145, 271–282

scholarly journals Positive, But Not Negative Feedback Actions of Estradiol in Adult Female Mice Require Estrogen Receptor α in Kisspeptin Neurons

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1111-1120 ◽  
Author(s):  
Sharon L. Dubois ◽  
Maricedes Acosta-Martínez ◽  
Mary R. DeJoseph ◽  
Andrew Wolfe ◽  
Sally Radovick ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Adult Female ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Estrogen Receptor Α ◽  
Female Mice ◽  
Lh Secretion ◽  
Express Estrogen Receptor ◽  
Specific Deletion

Abstract Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell–specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both.

scholarly journals Kisspeptin, Neurokinin B, and Dynorphin Act in the Arcuate Nucleus to Control Activity of the GnRH Pulse Generator in Ewes

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4259-4269 ◽  
Author(s):  
Robert L. Goodman ◽  
Stanley M. Hileman ◽  
Casey C Nestor ◽  
Katrina L. Porter ◽  
John M. Connors ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Afferent Input ◽  
Pulse Generation ◽  
Orphanin Fq ◽  
Neurokinin B ◽  
Control Activity ◽  
Kndy Neurons ◽  
Lh Secretion

Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation, with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting as start and stop signals, respectively. In this study, we tested this hypothesis by determining the actions, if any, of four neurotransmitters found in KNDy neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion using local administration of agonists and antagonists to receptors for these transmitters in ovariectomized ewes. We also obtained evidence that GnRH-containing afferents contact KNDy neurons, so we tested the role of two components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this antagonist produced a modest transitory decrease in LH pulse frequency. An antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and an antagonist to the receptor for dynorphin both increased pulse frequency. In contrast, antagonists to GnRH receptors, orphanin-FQ receptors, and the N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion. We thus conclude that the KNDy neuropeptides act in the arcuate nucleus to control episodic GnRH secretion in the ewe, but afferent input from GnRH neurons to this area does not. These data support the proposed roles for NKB and dynorphin within the KNDy neural network and raise the possibility that kisspeptin contributes to the control of GnRH pulse frequency in addition to its established role as an output signal from KNDy neurons that drives GnRH pulses.

Changes in FSH and the pulsatile secretion of LH during treatment of ewes with bovine follicular fluid throughout the luteal phase of the oestrous cycle

1986 ◽  
Vol 111 (2) ◽  
pp. 317-327 ◽  
Author(s):  
J. M. Wallace ◽  
A. S. McNeilly
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Treatment Cycle ◽  
Day Treatment ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Feedback Effects ◽  
Blood Samples ◽  
Three Stages ◽  
Lh Secretion

ABSTRACT Treatment of Damline ewes with twice-daily i.v. injections of bovine follicular fluid during the luteal phase for 10 or 2 days before prostaglandin-induced luteolysis resulted in a delay in the onset of oestrous behaviour and a marginal increase in ovulation rate. During the treatment cycle, blood samples were withdrawn at 15-min intervals for 25 h from 08.00 h on days 1, 6 and 10 (day 0 = oestrus). At all three stages of the luteal phase, plasma FSH concentrations were suppressed relative to controls 3 h after the 09.00 h injection of follicular fluid and remained low until 06.00 h on the following day. In the 10-day treatment group LH pulse amplitude was significantly greater than that of controls on days 6 and 10. Pulse frequency remained high throughout treatment and was significantly higher relative to controls on day 10 despite normal progesterone levels. The results suggest that the higher pulsatile LH secretion during the luteal phase is due to reduced negative feedback effects of oestradiol occurring as a result of the follicular fluid-induced reduction in FSH. J. Endocr. (1986) 111, 317–327

Pulsatile secretion of inhibin, oestradiol and androstenedione by the ovary of the sheep during the oestrous cycle

1990 ◽  
Vol 126 (3) ◽  
pp. 385-393 ◽  
Author(s):  
B. K. Campbell ◽  
G. E. Mann ◽  
A. S. McNeilly ◽  
D. T. Baird
Keyword(s):  
Luteal Phase ◽  
Venous Blood ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Blood Samples ◽  
Early Follicular Phase ◽  
Lh Secretion ◽  
Late Follicular Phase

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

Changes in the secretion of LH pulses, FSH and prolactin during the preovulatory phase of the oestrous cycle of the ewe and the influence of treatment with bovine follicular fluid during the luteal phase

1988 ◽  
Vol 116 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J. M. Wallace ◽  
G. B. Martin ◽  
A. S. McNeilly
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Ovarian Follicles ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Ovulation Rate ◽  
The Other ◽  
Lh Secretion

ABSTRACT It has previously been shown that treatment of ewes with bovine follicular fluid (bFF) throughout the luteal phase of the oestrous cycle lowers plasma levels of FSH but increases the frequency and amplitude of the pulses of LH. Under these conditions, ovarian follicles grow to a maximum diameter of 2·7 mm and have a reduced capacity to release oestradiol. We have examined the nature of the gonadotrophin signals controlling follicular development in the normally cycling ewe and have investigated the effects of previous exposure to bFF on these signals and the follicular responses to them. Control ewes (n = l) were injected i.v. with 9 ml bovine serum and treated ewes were injected with 9 ml bFF, twice daily from days 1 to 10 of the luteal phase (day 0 = oestrus). The ewes were injected with prostaglandin analogue on day 11 of the cycle to induce luteolysis and the gonadotrophin patterns were studied in blood sampled from these animals every 10 min for up to 72 h during the subsequent follicular phase. Following luteolysis (and the end of bFF treatment), LH pulse frequency increased rapidly in both groups and reached 1 pulse/h within 6 h. Thereafter, pulse frequency increased marginally and reached 1 pulse/50 min by the onset of the LH surge. This pattern was not affected by previous treatment with bFF. In the control ewes, the amplitude of the LH pulses did not change significantly following luteolysis or at any time during the follicular phase, while the levels of FSH declined slowly until the onset of the surge. In the treated ewes, on the other hand, there was an immediate increase in both LH pulse amplitude and the concentration of FSH immediately after the end of bFF treatment at luteolysis, and they remained above control levels for 24 and 16 h respectively. Plasma prolactin levels did not appear to change around the time of luteolysis but showed a marked and significant diurnal rhythm (nadir around noon and peak around midnight) in both groups. The concentrations of prolactin were significantly (P<0·001) lower and the preovulatory peak was delayed and reduced in the bFF-treated ewes relative to controls. The onset of oestrus was also significantly (P<0·01) delayed by bFF treatment, but the ovulation rates did not differ between the groups. Furthermore, comparisons within or between groups revealed no significant relationships between any of the variables of plasma LH secretion during the follicular phase and the subsequent ovulation rate. These observations provide a complete description of gonadotrophin patterns during the follicular phase of the ewe and confirm the suggestion that an increase in LH pulse frequency is the major driving force behind the follicular growth that ultimately leads to ovulation. On the other hand, it appears most unlikely that the pattern of LH secretion during the follicular phase has any influence on ovulation rate. The levels of FSH declined in the period leading up to the preovulatory surge, presumably as a consequence of rising peripheral levels of oestrogen (and/or inhibin). We also expected LH pulse amplitude to decline during the follicular phase because it has been proposed that pulse amplitude is also controlled by oestrogen. The absence of any significant fall in amplitude suggests that hypotheses about the control of LH secretion drawn from studies with ovariectomized ewes require further verification in the intact ewe. The effect of bFF on prolactin levels probably reflects the low rates of secretion of oestradiol by the small ovarian follicles in these ewes. J. Endocr. (1988) 116, 123–135

scholarly journals Estrogen-Negative Feedback and Estrous Cyclicity Are Critically Dependent Upon Estrogen Receptor-α Expression in the Arcuate Nucleus of Adult Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2986-2995 ◽  
Author(s):  
Shel-Hwa Yeo ◽  
Allan E. Herbison
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Arcuate Nucleus ◽  
Critical Role ◽  
Estrogen Receptor Α ◽  
Feedback Mechanism ◽  
Neuron Activity ◽  
Female Mice ◽  
Negative Feedback Mechanism ◽  
Estrous Cyclicity

The location and characteristics of cells within the brain that suppress GnRH neuron activity to contribute to the estrogen-negative feedback mechanism are poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP recombination in estrogen receptor-α (ERα) floxed mice (ERαflox/flox), we aimed to examine the role of ERα-expressing neurons located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism. Bilateral injection of AAV-Cre into the ARN of ERαflox/flox mice (n = 14) resulted in the time-dependent ablation of up to 99% of ERα-immunoreactive cell numbers throughout the rostrocaudal length of the ARN. These mice were all acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous. Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight was not altered in ERαflox/flox mice. After ovariectomy, a significant increment in LH secretion was observed in all genotypes, although its magnitude was reduced in ERαflox/flox mice. Acute and chronic estrogen-negative feedback were assessed by administering 17β-estradiol to mice as a bolus (LH measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later). This demonstrated that chronic estrogen feedback was absent in ERαflox/flox mice, whereas the acute feedback was normal. These results reveal a critical role for ERα-expressing cells within the ARN in both estrous cyclicity and the chronic estrogen negative feedback mechanism in female mice. This suggests that ARN cells provide a key indirect, transsynpatic route through which estradiol suppresses the activity of GnRH neurons.

Seasonal and steroid-dependent effects on the modulation of LH secretion in the ewe by intracerebroventricularly administered β-endorphin or naloxone

1989 ◽  
Vol 122 (2) ◽  
pp. 509-517 ◽  
Author(s):  
R. J. E. Horton ◽  
H. Francis ◽  
I. J. Clarke
Keyword(s):  
Breeding Season ◽  
Luteal Phase ◽  
Pulse Frequency ◽  
Opioid Peptide ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Opioid Antagonist ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Lh Secretion

ABSTRACT The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 μl), 100 μg naloxone or 10 μg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 μg β-endorphin(1–27), a purported endogenous opioid antagonist. In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 μg/l to less than 1 μg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 μg/l to undetectable levels, and neither saline nor naloxone affected LH secretion. During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion. These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect. Journal of Endocrinology (1989) 122, 509–517

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

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