Normal Reproductive function in male mice lacking pituitary kisspeptin receptor.

The anterior pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate gonadal development, gametogenesis and the secretion of the gonadal steroid hormones. The gonadotroph is primarily regulated by hypothalamic secretion of gonadotropin-releasing hormone (GnRH) from neurons of the rostral hypothalamus and is mediated by GnRH receptor signaling. Kisspeptin (KISS1)/kisspeptin receptor (KISS1R) signaling in GnRH neurons plays an essential role in reproductive function. As the kisspeptin receptor is present in the pituitary, kisspeptin signaling via the Kiss1r may regulate reproductive function at the level of pituitary. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO male and females have normal genital development, puberty onset, and fertility. Females have normal LH, FSH and estradiol while males had significantly increased basal serum FSH levels with no differences in basal serum LH, or testosterone levels. Overall, these findings indicate that the pituitary KISS1R does not play a role in male reproduction.

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Effects of Chronic Hyperghrelinemia on Puberty Onset and Pregnancy Outcome in the Rat

Endocrinology ◽

10.1210/en.2004-1622 ◽

2005 ◽

Vol 146 (7) ◽

pp. 3018-3025 ◽

Cited By ~ 98

Author(s):

R. Fernández-Fernández ◽

V. M. Navarro ◽

M. L. Barreiro ◽

E. M. Vigo ◽

S. Tovar ◽

...

Keyword(s):

Pregnancy Outcome ◽

Energy Homeostasis ◽

Reproductive Function ◽

Chronic Administration ◽

Serum Levels ◽

Male Rats ◽

Gestational Length ◽

Serum Lh ◽

Puberty Onset ◽

Key Aspects

Abstract Ghrelin, the endogenous ligand of the GH secretagogue receptor, has been recently involved in a wide array of biological functions, including signaling of energy insufficiency and energy homeostasis. On the basis of the proven reproductive effects of other regulators of energy balance, such as the adipocyte-derived hormone leptin, we hypothesized that systemic ghrelin may participate in the control of key aspects of reproductive function. To test this hypothesis, the effects of daily treatment with ghrelin were assessed in rats, pair-fed with control animals, in two relevant reproductive states, puberty and gestation, which are highly dependent on proper energy stores. Daily sc injection of ghrelin (0.5 nmol/12 h; between postnatal d 33 and 43) significantly decreased serum LH and testosterone levels and partially prevented balanopreputial separation (as an external index of puberty onset) in pubertal male rats. On the contrary, chronic administration of ghrelin to prepubertal females, between postnatal d 23 and 33, failed to induce major changes in serum levels of gonadotropins and estradiol, nor did it modify the timing of puberty, as estimated by the ages at vaginal opening and first estrus. Moreover, females treated with ghrelin at puberty subsequently displayed normal estrous cyclicity and were fertile. Conversely, ghrelin administration (0.5 nmol/12 h) during the first half of pregnancy (d 1–11) resulted in a significant decrease in pregnancy outcome, as estimated by the number of pups born per litter, without changes in the number of successful pregnancies at term or gestational length. Overall, our data indicate that persistently elevated ghrelin levels, as a putative signal for energy insufficiency, may operate as a negative modifier of key reproductive states, such as pregnancy and (male) puberty onset.

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Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Hormone Research in Paediatrics ◽

10.1159/000513787 ◽

2021 ◽

pp. 1-10

Author(s):

Lea Oelkers ◽

Mandy Vogel ◽

Agnes Kalenda ◽

Hans Christian Surup ◽

Antje Körner ◽

...

Keyword(s):

Socioeconomic Status ◽

Weight Status ◽

Pubertal Development ◽

Serum Levels ◽

Healthy Children ◽

Anthropometric Parameters ◽

Pubertal Onset ◽

Child Study ◽

Serum Lh ◽

Puberty Onset

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.

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Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-1069 ◽

2013 ◽

Vol 98 (11) ◽

pp. 4464-4474 ◽

Cited By ~ 19

Author(s):

C. N. Jayasena ◽

A. N. Comninos ◽

G. M. K. Nijher ◽

A. Abbara ◽

A. De Silva ◽

...

Keyword(s):

Menstrual Cycle ◽

Reproductive Function ◽

Reproductive Hormones ◽

Follicular Phase ◽

Hypothalamic Amenorrhea ◽

Healthy Women ◽

Lh Pulsatility ◽

Serum Lh ◽

Healthy Female ◽

Ultrasound Parameters

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

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ENDOCRINE STUDIES AND SUCCESSFUL TREATMENT IN A PATIENT WITH TRUE HERMAPHRODITISM

Acta Endocrinologica ◽

10.1530/acta.0.0910184 ◽

1979 ◽

Vol 91 (1) ◽

pp. 184-192

Author(s):

Evangelina Valdés ◽

Carlos Fernández del Castillo ◽

Raul Gutiérrez ◽

Fernando Larrea ◽

Martha Medina ◽

...

Keyword(s):

Chromosome Complement ◽

Reproductive Function ◽

External Genitalia ◽

Serum Testosterone ◽

Serum Levels ◽

Normal Children ◽

Serum Lh ◽

Genital Ambiguity ◽

And Gender ◽

Lh Rh

ABSTRACT A 12-year old, 46 XX true hermaphrodite born with genital ambiguity was studied and successfully treated. The serum LH and FSH profile resembled that of a pubertal normal individual, and LH-RH administration induced a normal LH response. Baseline testosterone serum levels were within the range for normal children. Exogenous HCG stimulation induced a significant serum testosterone increase up to values similar to those observed in normal post-pubertal males. Surgical examination disclosed the presence of bilateral ovotestis, normal Mullerian derivatives, epididymis, and vas deferens. A complete ovotestis with testicular predominance and the testicular portion of the contralateral ovotestis as well as the Wolffian derivatives, were removed. A further HCG stimulation 3 months after surgery, failed to induce serum testosterone increase. Spontaneous menarche was observed 6 months after surgery and ovulation was well documented. At present the patient has several characteristics of female sex including those of chromosome complement, gonad, internal and external genitalia, hormone levels and gender identity, thus demonstrating that treatment was successful and that reproductive function could be obtained. The finding of spontaneous ovulation following removal of the testicular portion suggests normal cyclic gonadotrophic release implying a difference between animal models and man in regard to hypothalamic virilization.

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Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control

Molecules ◽

10.3390/molecules23123071 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3071 ◽

Cited By ~ 9

Author(s):

Giustino Orlando ◽

Sheila Leone ◽

Claudio Ferrante ◽

Annalisa Chiavaroli ◽

Adriano Mollica ◽

...

Keyword(s):

Gene Expression ◽

Energy Homeostasis ◽

Hormone Secretion ◽

Reproductive Function ◽

Inhibitory Effect ◽

Bdnf Gene ◽

Appetite Control ◽

Hydroxyindoleacetic Acid ◽

Puberty Onset

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.

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Gnrh1-induced responses are indirect in female medaka Fsh cells

10.1101/763250 ◽

2019 ◽

Author(s):

Kjetil Hodne ◽

Romain Fontaine ◽

Eirill Ager-Wick ◽

Finn-Arne Weltzien

Keyword(s):

Patch Clamp ◽

Adult Female ◽

Reproductive Function ◽

Cell Types ◽

Gonadal Development ◽

Pituitary Cells ◽

Tissue Slices ◽

Lh Cells ◽

Different Cell Types

ABSTRACTReproductive function in vertebrates is stimulated by gonadotropin-releasing hormone (GnRH) that controls the synthesis and release of the two pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH, which regulates different stages of gonadal development, are produced by two different cell types in the fish pituitary, in contrast to mammals and birds, thus allowing the investigation of their differential regulation. In the present work, we show by fluorescentin situhybridization that Lh cells in adult female medaka express Gnrh receptors, whereas Fsh cells do not. This is confirmed by patch clamp recordings and cytosolic Ca2+measurements on dispersed pituitary cells, where Lh cells, but not Fsh cells, respond to Gnrh1 by increased action potential frequencies and cytosolic Ca2+levels. In contrast, both Fsh and Lh cells are able to respond electrically and by elevating the cytosolic Ca2+levels to Gnrh1 in brain-pituitary tissue slices. Using Ca2+uncaging in combination with patch clamp recordings and cytosolic Ca2+measurements, we show that Fsh and Lh cells form homo- and heterotypic networks in the pituitary. Taken together, these results show that the effects of Gnrh1 on Fsh release in adult female medaka is indirect, likely mediated via Lh cells.

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Evidence for increased tissue androgen sensitivity in neurturin knockout mice

Journal of Endocrinology ◽

10.1530/joe-13-0056 ◽

2013 ◽

Vol 218 (2) ◽

pp. 151-163 ◽

Cited By ~ 3

Author(s):

Ulla Simanainen ◽

Yan Ru (Ellen) Gao ◽

Reena Desai ◽

Mark Jimenez ◽

Jennifer Spaliviero ◽

...

Keyword(s):

Knockout Mice ◽

Structural Changes ◽

Reproductive Function ◽

Reproductive Organs ◽

Gnrh Analogue ◽

Accessory Glands ◽

Serum Lh ◽

Androgen Sensitivity ◽

In The Wild ◽

Circulating Levels

Neurturin (NTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family and signals through GDNF family receptor alpha 2 (GFRα2). We hypothesised that epithelial atrophy reported in the reproductive organs ofNtn(Nrtn)- andGfrα2(Gfra2)-deficient mice could be due to NTN affecting the hormonal environment. To investigate this, we compared the reproductive organs ofNtn- andGfrα2-deficient male mice in parallel with an analysis of their circulating reproductive hormone levels. There were no significant structural changes within the organs of the knockout mice; however, serum and intratesticular testosterone and serum LH levels were very low. To reconcile these observations, we tested androgen sensitivity by creating a dihydrotestosterone (DHT) clamp (castration plus DHT implant) to create fixed circulating levels of androgens, allowing the evaluation of androgen-sensitive endpoints. At the same serum DHT levels, serum LH levels were lower and prostate and seminal vesicle weights were higher in theNtnknockout (NTNKO) mice than in the wild-type mice, suggesting an increased response to androgens in the accessory glands and hypothalamus and pituitary of the NTNKO mice. Testicular and pituitary responsiveness was unaffected in the NTNKO males, as determined by the response to the human chorionic gonadotrophin or GNRH analogue, leuprolide, respectively. In conclusion, our results suggest that NTN inactivation enhances androgen sensitivity in reproductive and neuroendocrine tissues, revealing a novel mechanism to influence reproductive function and the activity of other androgen-dependent tissues.

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The utility of basal serum LH in prediction of central precocious puberty in girls

Acta Endocrinologica ◽

10.1530/eje-11-0720 ◽

2012 ◽

Vol 166 (2) ◽

pp. 295-299 ◽

Cited By ~ 36

Author(s):

Yehonatan Pasternak ◽

Michael Friger ◽

Neta Loewenthal ◽

Alon Haim ◽

Eli Hershkovitz

Keyword(s):

Precocious Puberty ◽

Predictive Value ◽

Central Precocious Puberty ◽

Stimulation Test ◽

Breast Development ◽

Basal Serum ◽

Serum Lh ◽

Before And After ◽

Design And Methods ◽

Prepubertal Girls

ObjectiveThe mainstay of distinction between prepubertal girls and girls who are suspected of having central precocious puberty (CPP) is based on gonadotropin measurements after a GnRH stimulation test to evaluate hypothalamic–pituitary–gonadal axis maturity. The objective of this study was to determine whether a single basal gonadotropin measurement carries a useful predictive value in verifying or refuting the diagnosis of CPP.Design and methodsBasal serum LH and FSH were measured by a chemiluminescent immunometric assay in a cohort of girls who had been evaluated for CPP before and after GnRH stimulation test. Peak LH levels higher than 5 IU/l were considered a pubertal response.ResultsEighty girls with suspected breast development before 8 years of age were enrolled to the study, out of whom 42 had CPP.Low basal serum LH (≤0.1 IU/l) was sufficient to rule out the diagnosis of CPP in 94.7% of the 38 prepubertal girls; the sensitivity of basal LH levels for this purpose was only 64%. The basal FSH and the basal LH to FSH ratio achieved less efficient predictive value with 76 and 71% sensitivity and 73 and 86% specificity respectively.ConclusionA single basal LH measurement may be adequate to confirm but not to refute the presence of CPP in most of the girls who are evaluated for early pubertal signs.

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Infestation of the squat lobster Munida gregaria (Anomura: Galatheidae) by Pseudione galacanthae (Isopoda: Bopyridae) in San Jorge Gulf, Argentina

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315410000639 ◽

2010 ◽

Vol 91 (8) ◽

pp. 1681-1688 ◽

Cited By ~ 2

Author(s):

Martín Varisco ◽

Julio Vinuesa

Keyword(s):

Gonad Development ◽

Reproductive Potential ◽

Reproductive Function ◽

Gonadal Development ◽

Squat Lobster ◽

By Catch ◽

Size Interval ◽

The Right ◽

Low Prevalence ◽

Squat Lobsters

We estimated the prevalence of the bopyrid Pseudione galacanthae parasitizing the population of the squat lobster Munida gregaria in San Jorge Gulf and analysed some aspects concerning the effect of the parasite on host reproductive potential. The relationship between the development stages of the parasite and the host size was also analysed. The squat lobsters were caught as by-catch in the coastal area of the gulf from vessels operating in the fisheries of hake Merluccius hubbsi, southern king crab Lithodes santolla and Argentine red shrimp Pleoticus muelleri. The samples were collected between October 1997 and June 2009. In the laboratory, squat lobsters were sexed and the length of their carapace was measured. In males, the length of the right cheliped was recorded and gonadal development was examined. In females, the size and number of carried eggs were determined and the length of the pleopods III, IV and V were measured. All squat lobsters parasitized exhibit a gross bulge in the right side of carapace. Prevalence ranged between 0 and 1.43% (N = 21,519). No significant differences in prevalence were found for sexes, depths and seasons. The prevalence was higher for the size interval 7–10 mm CL (0.79%) than for the rest of the intervals. Parasitism had no effect on the secondary sex characters. Parasitized males displayed gonad development. There was no difference in prevalence between ovigerous and non-ovigerous squat-lobster females. Parasitized females had smaller eggs than non-parasitized ones, but their fecundity was similar. The linear relationship between the parasite and host sizes and the presence of larvae and immature stages of P. galacanthae in small-sized squat lobsters suggest that the host is infected early in its development. The low prevalence could be related to oceanographic conditions which favour larval dispersal of the parasite and host. The infestation by P. galacanthae has little impact on the M. gregaria population, mostly due to the low prevalences of infestation and the minor impact in reproductive function.

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Effect of premating injections of insulin on fertility and prolificacy of ewes

Canadian Journal of Animal Science ◽

10.4141/cjas91-028 ◽

1991 ◽

Vol 71 (1) ◽

pp. 241-244 ◽

Cited By ~ 3

Author(s):

R. N. Kirkwood ◽

P. A. Thacker ◽

R. S. Korchinski ◽

B. Laarveld ◽

A. Gonzalez

Keyword(s):

Key Words ◽

Pregnancy Rate ◽

Litter Size ◽

Lh Surge ◽

Basal Serum ◽

Acting Insulin ◽

Serum Lh ◽

Key Words Insulin ◽

Long Acting

Ninety-six Suffolk ewes received daily injections of either long-acting insulin (1.0 IU kg−1) or saline for 3 consecutive days after introduction of rams. Basal serum LH concentrations were higher (P < 0.05) in insulin-treated ewes (P < 0.05) but concentrations of estradiol-17B and the magnitude of the preovulatory LH surge were unaffected. Interval to breeding, pregnancy rate and subsequent litter size were not influenced by treatment (66.6 vs. 63.3 h, 69 vs. 74% and 1.65 vs. 1.69 for insulin and saline-injected ewes, respectively). Key words: Insulin, sheep, fertility, prolificacy

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