Kisspeptin induces LH release and ovulation in an induced ovulator†

Abstract Kisspeptin has been implicated in the ovulatory process of several species of spontaneous ovulators but in only one induced ovulator. In contrast, NGF in semen is the principal trigger of ovulation in other species of induced ovulators—camelids. We tested the hypotheses that kisspeptin induces luteinizing hormone (LH) secretion in llamas through a hypothalamic mechanism, and kisspeptin neurons are the target of NGF in its ovulation-inducing pathway. In Experiment 1, llamas were given either NGF, kisspeptin, or saline intravenously, and LH secretion and ovulation were compared among groups. All llamas treated with NGF (5/5) or kisspeptin (5/5) had an elevation of LH blood concentrations after treatment and ovulated, whereas none of the saline group did (0/5). In Experiment 2, llamas were either pretreated with a gonadotropin-releasing hormone (GnRH) receptor antagonist or saline and treated 2 h later with kisspeptin. Llamas pretreated with saline had elevated plasma LH concentrations and ovulated (6/6) whereas llamas pretreated with cetrorelix did not (0/6). In Experiment 3, we evaluated the hypothalamic kisspeptin-GnRH neuronal network by immunohistochemistry. Kisspeptin neurons were detected in the arcuate nucleus, the preoptic area, and the anterior hypothalamus, establishing synaptic contacts with GnRH neurons. We found no colocalization between kisspeptin and NGF receptors by double immunofluorescence. Functional and morphological findings support the concept that kisspeptin is a mediator of the LH secretory pathway in llamas; however, the role of kisspeptins in the NGF ovulation-inducing pathway in camelids remains unclear since NGF receptors were not detected in kisspeptin neurons in the hypothalamus.

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Involvement of norepinephrine in pituitary LH release induced by oestradiol in vitro

Acta Endocrinologica ◽

10.1530/acta.0.1070199 ◽

1984 ◽

Vol 107 (2) ◽

pp. 199-203

Author(s):

A. Miyake ◽

K. Tasaka ◽

T. Aono

Keyword(s):

Oestrous Cycle ◽

Female Rats ◽

Direct Effects ◽

Significant Release ◽

Lh Release ◽

Lh Secretion ◽

Perifusion System ◽

Double Chamber

Abstract. The direct effects of oestradiol-17β (E2) on pituitary luteinizing hormone (LH) release and the role of norepinephrine (NE) in E2-induced gonadtrophin release were examined in a sequential double chamber perifusion system by perifusing the mediobasal hypothalami (MBH) and/or pituitaries excised from normally cycling female rats. Administration of E2 induced significant release (70–160% increase, P < 0.05) of LH from the pituitary of rats in pro-oestrus, but not in other stages of the oestrous cycle. When the MBH and the pituitary were perifused in sequence, E2 induced significant release of LH in all stages of the oestrous cycle except oestrus. When the pituitary from rats in dioestrus II was perifused alone with medium containing 200 ng/ml NE, significant release of LH (80–170% increase, P < 0.05) was observed after the administration of E2. The E2-induced LH release in pro-oestrus was completely abolished by perifusion with medium containing diethyldithiocarbamate, an inhibitor of NE synthesis. These findings suggest that NE may be involved in changes of pituitary responsiveness in LH secretion to oestrogen during the rat oestrous cycle.

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Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse

Endocrinology ◽

10.1210/en.2019-00195 ◽

2019 ◽

Vol 160 (10) ◽

pp. 2453-2463 ◽

Cited By ~ 2

Author(s):

Silvia León ◽

Chrysanthi Fergani ◽

Rajae Talbi ◽

Serap Simavli ◽

Caroline A Maguire ◽

...

Keyword(s):

Sex Steroids ◽

Neurokinin A ◽

Central Control ◽

Gnrh Release ◽

Lh Release ◽

Timing Of Puberty ◽

Puberty Onset ◽

Lh Secretion

Abstract The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.

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Adrenal progesterone facilitates the negative feedback of oestrogen on LH release in ovariectomized rats

Journal of Endocrinology ◽

10.1677/joe.0.1390253 ◽

1993 ◽

Vol 139 (2) ◽

pp. 253-258 ◽

Cited By ~ 7

Author(s):

A. M. Salicioni ◽

R. W. Carón ◽

R. P. Deis

Keyword(s):

Ovariectomized Rats ◽

Adrenal Steroids ◽

Serum Progesterone ◽

Oestrogen Treatment ◽

Ovx Rats ◽

Serum Lh ◽

Oestradiol Benzoate ◽

Lh Release ◽

Lh Secretion

ABSTRACT There is evidence that the adrenals play a role in the regulation of the synthesis and release of gonadotrophins in various vertebrates. The aim of this study was to determine the part played by adrenal steroids, with special reference to progesterone, on the concentration of LH in ovariectomized (OVX) and oestrogen-primed rats. OVX rats received a single s.c. injection of vehicle or oestradiol benzoate (OB, 20 μg/rat). This day was designated as day 0. Three or four days later (day 3–day 4), the rats were treated with mifepristone (10 mg/kg) or with two doses of progesterone antiserum and blood samples were obtained at 13.00 and 18.00 h. OB treatment of OVX rats reduced serum LH at 13.00 h and 18.00 h on day 3 but only at 13.00 h on day 4. The administration of mifepristone at 08.00 h to OVX and oestrogen-treated rats induced a significant increase in serum LH at 18.00 h on days 3 and 4, without modifying the values at 13.00 h. When mifepristone was given at 13.00 h a much larger increase in serum LH was obtained at 18.00 h. In OVX and oestrogen-treated rats, adrenalectomy on day 2 (08.00–09.00 h) induced an increase in serum LH at 18.00 h similar to that observed in the OVX and oestrogen-primed rats after mifepristone treatment. In order to determine the specificity of the effect of mifepristone, a group of OVX and oestrogentreated rats was injected with progesterone antiserum at 08.00 and 13.00 h on day 3. Serum LH concentrations at 13.00 and 18.00 h on day 3 were similar to values obtained in OVX rats treated with oestrogen and mifepristone. Serum progesterone was measured at 08.00 and 13.00 h in OVX and OVX and oestrogenprimed rats. At both times, values were similar in OVX rats but oestrogen treatment significantly increased serum progesterone levels. The important role of adrenal progesterone on the regulation of LH secretion in OVX and oestrogen-primed rats is evident from these results. Blocking progesterone action at the receptor level, we showed that OB significantly increased LH values at 18.00 h. On the basis of these studies it is tempting to speculate on the possibility of an inhibitory or stimulatory effect of oestrogen on serum LH concentration in OVX rats, according to the presence or absence of adrenal progesterone action. Journal of Endocrinology (1993) 139, 253–258

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Opioidergic control of luteinizing hormone secretion in the female rabbit: influence of age on the response to naloxone

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y88-007 ◽

1988 ◽

Vol 66 (1) ◽

pp. 38-42 ◽

Cited By ~ 2

Author(s):

E. V. YoungLai ◽

M. Wilkinson ◽

N. Thompson ◽

A. Byrne

Keyword(s):

Luteinizing Hormone ◽

Hormone Secretion ◽

Elevated Serum ◽

Luteinizing Hormone Secretion ◽

Serum Progesterone ◽

Female Rabbit ◽

Lh Release ◽

Lh Secretion ◽

Normal Inhibition

To examine the role of opioid neurons on luteinizing hormone (LH) secretion in the female rabbit, we determined LH release at timed intervals after naloxone administration to rabbits aged 25–150 days. The LH response to naloxone (10 mg/kg) was not significantly elevated until day 43 when LH rose 76–113% above basal levels at 40–80 min. In 56-day-old females the corresponding increase was 160% at 15 min and in 65- to 67-day-olds it was 154%. From 70 to 80 days of age the LH response was blunted and no significant elevations could be elicited. By contrast, naloxone-induced LH increases were again evident when rabbits were older than 100 days. At all ages no significant change in FSH concentrations was observed. In the adult females, naloxone at 2.5, 5, and 10 mg/kg caused increases in LH secretion which occasionally were high enough to induce ovulation as exemplified by elevated serum progesterone 4 days later. These data suggest that opioid peptides may be involved in the prepubertal rise in LH and in the normal inhibition of adult secretion in the female rabbit.

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Hypothalamic involvement and the role of progesterone in the NGF-induced LH surge pathway

Reproduction ◽

10.1530/rep-20-0647 ◽

2021 ◽

Author(s):

Rodrigo A Carrasco ◽

Carlos E Leonardi ◽

Sergio Pezo ◽

Gregg P Adams

Keyword(s):

Secretory Pathway ◽

High Plasma ◽

Saline Group ◽

Plasma Progesterone ◽

Lh Surge ◽

Treatment Groups ◽

Gnrh Neurons ◽

Series Of Experiments ◽

Expression Marker

To elucidate the mechanism by which nerve growth factor (NGF) influences the LH secretory pathway in camelids, a series of experiments were done to determine the involvement of the hypothalamus (Experiment 1), the role of GnRH neurons (Experiment 2), and the effect of progesterone (Experiment 3) on the NGF-induced LH surge and ovulation in llamas. In Experiment 1, the declining phase of the NGF-induced LH surge was used to determine if the decline is a result of pituitary depletion or hypothalamic unresponsiveness. Female llamas were treated with NGF and, 7 hours later, assigned to three groups and given a second dose of NGF (n = 5), a dose of GnRH (n = 5), or saline (n = 6). The LH response was attenuated after the second dose of NGF vs. GnRH. In Experiment 2, Fos expression (marker of neuronal activation) in GnRH neurons was examined in the hypothalamus of llamas after NGF or saline treatment (n = 3 per group). Despite an LH surge in the NGF group but not in the saline group, no differences were detected between groups in Fos/GnRH co-expression. In Experiment 3, llamas in low-, medium-, and high-plasma progesterone groups (n = 4 per group) were treated with NGF. The NGF-induced LH surge did not differ among treatment groups. Results from the present study show that the induction of a preovulatory LH surge by NGF may be controlled by a novel pathway involving GnRH neuro-terminals downstream of the hypothalamus and is independent of progesterone influence.

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Patterns of spontaneous LH release in normo- and hyperprolactinaemic women

Acta Endocrinologica ◽

10.1530/acta.0.0970305 ◽

1981 ◽

Vol 97 (3) ◽

pp. 305-310 ◽

Cited By ~ 14

Author(s):

Maire T. Buckman ◽

Glenn T. Peake ◽

Laxima Srivastava ◽

Josephine Morris ◽

Barry David ◽

...

Keyword(s):

Sampling Period ◽

Normal Subjects ◽

Plasma Prolactin ◽

Early Follicular Phase ◽

Lh Release ◽

Normal Women ◽

17 Hydroxyprogesterone ◽

Group Sex ◽

Lh Secretion

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

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Steroid effects on the in vitro LH secretion from pituitary cells of sexually immature carp (Cyprinus carpio L.) under the influence of naltrexone and morphine

Czech Journal of Animal Science ◽

10.17221/131/2009-cjas ◽

2010 ◽

Vol 55 (No. 6) ◽

pp. 250-257

Author(s):

M. Sokolowska-Mikolajczyk ◽

M. Socha ◽

P. Epler

Keyword(s):

Cyprinus Carpio ◽

Sex Steroids ◽

Pituitary Cells ◽

Control Medium ◽

Opioid Agonist ◽

Carp Cyprinus Carpio ◽

Lh Release ◽

Lh Secretion

Dispersed cells from sexually immature carp (footlings) pituitaries were exposed to estradiol (E2) or testosterone (T) (both at 3 × 10–8 M) in the presence of opioid receptor antagonist naltrexone (10–8 or 10–6 M) and/or agonist – morphine (10–8 or 10–6 M). Naltrexone alone at 10–6 M increased the LH level as compared with the control. Morphine (10–8 or 10–6 M), T and E2 had no influence on LH levels. The combination of T with naltrexone (10–8 M) stimulated LH release if compared with the control or with T alone. Morphine (both concentrations) with T caused significantly higher LH secretion than the control medium and T alone. Estradiol with naltrexone (10–8 and 10–6 M) had no influence on LH concentration. In media with E2 and morphine (10–8 M) LH levels were higher than in the control and estradiol alone. The results show that in common carp sex steroids affect the response of pituitary cells to opioid agonist or antagonist giving an evidence on the role of steroids in LH release mediated by the opioid system.

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Effect of acute immunoneutralization of endogenous leptin on prolactin and LH secretion during the afternoon of pro-oestrus or in steroid-treated ovariectomized female rats

Reproduction ◽

10.1530/reprod/118.1.39 ◽

2000 ◽

pp. 39-45 ◽

Cited By ~ 9

Author(s):

LC Gonzalez ◽

L Pinilla ◽

M Tena-Sempere ◽

C Dieguez ◽

FF Casanueva ◽

...

Keyword(s):

Prolactin Secretion ◽

Female Rats ◽

Ovariectomized Rats ◽

Rabbit Serum ◽

Normal Rabbit Serum ◽

Blood Samples ◽

Lh Release ◽

Lh Secretion

Recent data indicate that leptin is involved in the control of reproductive function. Experiments were carried out to analyse the role of endogenous leptin in the regulation of LH and prolactin secretion during the afternoon of pro-oestrus and that induced by ovarian steroids in ovariectomized rats. In the first experiment, cyclic female rats were implanted with intra-auricular and intracerebroventricular (i.c.v.) cannulae and, at pro-oestrus, were injected (i.c.v.) with 10 microliters normal rabbit serum or leptin antiserum (at 13:00 and 14:00 h). Blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the second experiment, female rats in pro-oestrus were injected with normal rabbit serum or leptin antiserum at 16:00 and 18:00 h and blood samples were taken every 10 min between 18:00 and 20:00 h. In the third experiment, adult female rats that had been ovariectomized 2 weeks before were implanted with intra-auricular and i.c.v. cannulae and treated with oestradiol benzoate (30 micrograms s.c.) at 10:00 h and progesterone (2 mg s.c.) 48 h later. Normal rabbit serum (10 microliters) or leptin antiserum (10 microliters) were injected (i.c.v.) at 13:00 and 14:00 h, and blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the fourth experiment, hemipituitaries from ovariectomized steroid-treated female rats were incubated in the presence of leptin116-130 (an active fragment of the native molecule), GnRH or leptin + GnRH. Prolactin and LH secretion during the afternoon of pro-oestrus in females treated with leptin antiserum was similar to that observed in animals injected with normal rabbit serum. In ovariectomized female rats, the steroid-induced LH surge increased slightly after administration of leptin antiserum, whereas the prolactin surge remained unchanged. In vitro, leptin116-130 (10(-5) to 10(-8) mol l-1) inhibited LH secretion and modulated the effect of GnRH on LH release, depending on the concentration of GnRH: leptin116-130 (10(-6) mol l-1) reduced the effectiveness of 10(-7) mol GnRH l-1 and increased that of 10(-9) mol GnRH l-1. In conclusion, these experiments indicate that acute immunoneutralization of endogenous leptin does not interfere with spontaneous or steroid-induced LH and prolactin surges. In addition, the finding that leptin116-130 inhibited LH release and modulated the effectiveness of GnRH in vitro provides evidence of the direct modulatory role of leptin on LH secretion acting at the pituitary.

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Effects of non-steroidal gonadal factors on LH secretion in female common carp during the reproductive cycle

Czech Journal of Animal Science ◽

10.17221/337-cjas ◽

2008 ◽

Vol 53 (No. 9) ◽

pp. 398-403

Author(s):

J. Chyb ◽

T. Mikolajczyk ◽

M. Sokolowska-Mikolajczyk ◽

M. Socha ◽

P. Szczerbik ◽

...

Keyword(s):

Common Carp ◽

Reproductive Cycle ◽

Inhibitory Effect ◽

Gonad Maturity ◽

Lh Release ◽

Gonadal Recrudescence ◽

Lh Secretion

The aim of this study was to evaluate the effects of recombinant human inhibin A, recombinant human activin A and desteroidized ovarian extract on LH secretion in vitro and in vivo in female common carp during different stages of reproductive cycle. Inhibin stimulated spontaneous as well as GnRH-stimulated LH release in vivo in fish during gonadal recrudescence. This hormone did not have an influence on spontaneous LH secretion in the periovulatory period, but had a slightly inhibitory effect on GnRH-stimulated LH release in this stage of gonad maturity. Activin decreased spontaneous LH secretion during gonadal recrudescence and increased LH secretion before ovulation, having no effects on GnRH-stimulated LH release during both stages of gonad maturity. The desteroidized ovarian extract failed to modify spontaneous LH secretion, but decreased GnRH-stimulated LH release during recrudescence and especially before ovulation. It is to conclude that these data suggest the differential role of inhibin/activin as substances in the regulation of LH secretion in common carp females.

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Vasoactive intestinal peptide indirectly elicits pituitary LH secretion independent of GnRH in female zebrafish

Endocrinology ◽

10.1210/endocr/bqab264 ◽

2022 ◽

Author(s):

Sakura Tanaka ◽

Nilli Zmora ◽

Berta Levavi-Sivan ◽

Yonathan Zohar

Keyword(s):

Vasoactive Intestinal Peptide ◽

Mature Female ◽

Mrna Levels ◽

Lh Release ◽

Lh Cells ◽

Female Zebrafish ◽

Lh Secretion ◽

Sexually Mature

Abstract Vasoactive intestinal peptide (Vip) regulates luteinizing hormone (LH) release through the direct regulation of gonadotropin-releasing hormone (GnRH) neurons at the level of the brain in female rodents. However, little is known regarding the roles of Vip in teleost reproduction. Although GnRH is critical for fertility through the regulation of LH secretion in vertebrates, the exact role of the hypophysiotropic GnRH (GnRH3) in zebrafish is unclear since GnRH3 null fish are reproductively fertile. This phenomenon raises the possibility of a redundant regulatory pathway(s) for LH secretion in zebrafish. Here, we demonstrate that VipA (homologues of mammalian Vip) both inhibits and induces LH secretion in zebrafish. Despite the observation that VipA axons may reach the pituitary proximal pars distalis including LH cells, pituitary incubation with VipA in vitro, and intraperitoneal injection of VipA, did not induce LH secretion and lhβ mRNA expression in sexually mature females, respectively. On the other hand, intracerebroventricular administration of VipA augmented plasma LH levels in both wild type and gnrh3-/- females at 1 hour post-treatment, with no observed changes in pituitary GnRH2 and GnRH3 contents and gnrh3 mRNA levels in the brains. While VipA’s manner of inhibition of LH secretion has yet to be explored, the stimulation seems to occur via a different pathway than GnRH3, dopamine, and E2 in regulating LH secretion. The results indicate that VipA induces LH release possibly by acting with or through a non-GnRH factor(s), providing proof for the existence of functional redundancy of LH release in sexually mature female zebrafish.

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