Luteinizing Hormone Response Research Articles

Impact of varicocele on biological markers of gonadal function.

The aim of this study is to evaluate the potential effect of varicocele in the hormonal and clinical profile of adolescents. Twenty adolescents at Tanner stage 4-5 with left varicocele were studied and compared with a control group of 20 healthy adolescents. All patients underwent ultrasonographic testicular volumetry as well as hormonal evaluation of inhibin B, testosterone, baseline and gonadotropin-releasing hormone stimulated, follicle-stimulating hormone as well as luteinizing hormone. Statistical analysis was performed using the student's t test with p value <0.05 taken as statistical significant. Patients with varicocele showed reduced levels of inhibin B compared to controls and a significant reduction in the testicular volume on the affected side. The response of luteinizing hormone to gonadotropin-releasing hormone stimulation was significantly higher in the varicocele group compared to the control group. Furthermore a significant inverse relationship of inhibin B compared to follicle-stimulating hormone was noted. Serum inhibin B levels could represent a useful marker of Sertoli cell damage caused by varicocele.

Evidence that Neurokinin B Controls Basal Gonadotropin-Releasing Hormone Secretion but Is Not Critical for Estrogen-Positive Feedback in Sheep

Background: Loss-of-function mutations in genes encoding kisspeptin or neurokinin B (NKB) or their receptors cause infertility. NKB is coproduced in kisspeptin neurons in the arcuate nucleus (ARC), and these neurons also produce the NKB receptor (NK3R), allowing autosynaptic function. We tested the hypothesis that NKB action in ARC kisspeptin neurons is aligned with increased pulsatile secretion of luteinizing hormone (LH) and/or activation of the estrogen-induced LH surge in ewes. Methods: Using in situ hybridization and immunohistochemistry, we examined NKB expression in kisspeptin neurons during the ovine estrous cycle. We infused kisspeptin, senktide (an NK3R agonist), or dynorphin into the lateral ventricle during the luteal phase of the estrous cycle to determine effects on pulsatile LH secretion. Finally, we examined the effect of an NK3R antagonist (MRK-08) in ovariectomized ewes. Results: NKB (Tac3) mRNA expression in mid-ARC kisspeptin neurons was elevated during the mid-to-late follicular phase of the estrous cycle. The number of NKB-immunoreactive cells and NKB/kisspeptin terminals in the median eminence was similar during the estrous cycle. Kisspeptin and senktide increased LH pulse frequency and mean LH levels. Central MRK-08 infusion eliminated the LH pulses but did not prevent an estrogen-positive feedback on LH secretion. Conclusions: NKB expression in ARC kisspeptin neurons is upregulated during the late follicular phase of the estrous cycle, when the pulsatile secretion of gonadotropin-releasing hormone (GnRH)/LH is maximal. When GnRH/LH secretion is minimal, central senktide infusion induces LH secretion, similar to the response to kisspeptin. Although the increase in LH in response to senktide appeared surge-like, we did not observe any change in the surge following NK3R antagonist treatment. We conclude that NKB plays a role in increasing basal GnRH/LH pulsatility in the follicular phase of the cycle but is not essential for estrogen-induced positive feedback.

Luteinizing hormone, testosterone and total estrogens response to exogenous GnRH in crossbred bulls with differing semen quality

The present study aims to investigate the Luteinizing hormone (LH), testosterone and total estrogens response to exogenous gonadotropin-releasing hormone (GnRH) in adult crossbred bulls with differing semen quality. Fourteen adult crossbred bulls of differing semen quality were selected and treated with 10µg of GnRH (Buserelin acetate) intramuscularly. Blood samples of the bulls were collected at an interval of 30min commencing 1h prior to GnRH treatment until 4h post-GnRH treatment and thereafter, at an interval of 1h for the next 3h. The endocrine response in terms of peak values, area under the curve, and the time taken to attain peak values for LH, testosterone, and total estrogens were evaluated in all the bulls. The mean±SEM peak levels of LH, testosterone, and total estrogens were found to be 150±24.1, 5.3±0.69, and 0.07±0.01ng/mL, respectively. The mean±SEM area under the curve of LH, testosterone, and total estrogens were found to be 392±51.3, 23.5±3.4, and 0.32±0.04ng/mL×h, respectively. The relationships between hormonal responses (LH, testosterone, and total estrogens) and semen quality were analyzed using the linear regression method, which provided non-significant (P>0.05) results. This study indicated that the gonadal and pituitary hormonal response to single exogenous GnRH treatment may have no relationship with the semen quality of crossbred bulls.

Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty.

To clarify the impact of body mass index (BMI) on luteinizing hormone (LH) secretion in response to gonadorelin (GnRH) stimulation testing in girls diagnosed with idiopathic central precocious puberty (ICPP). Retrospective single-center cohort study was carried out in 865 confirmed ICPP girls who underwent GnRH stimulation tests. Pubertal development according to Tanner, sex hormone parameters, and LH secretion in response to GnRH-stimulation was compared. Around 609 girls were of normal weight (70.4%), while 168 children (19.4%) were overweight, and 88 (10.2%) were obese. Peak LH levels after GnRH were much higher in the normal-weight group, with a median of 9.1 mIU ml(-1) (interquartile 5.2-13.1), compared with the median peak LH in the overweight and obese groups (8.5 mIU ml(-1), interquartile 5.3-11.6, and 6.2 mIU ml(-1), interquartile 5.3-11.0, respectively P < 0.001 for all comparisons). Peak LH/FSH ratio was also lower in the obese group (median 0.6, interquartile 0.68-0.90) compared with the normal-weight (median 0.8, interquartile 0.61-1.11) and overweight (median 0.8, interquartile 0.64-0.92) groups. Higher BMI is associated with lower LH response to GnRH-stimulation testing in girls with ICPP. It is recommended that BMI should be considered when interpreting GnRH-stimulation tests.

Kisspeptin regulates tuberoinfundibular dopaminergic neurones and prolactin secretion in an oestradiol-dependent manner in male and female rats.

Prolactin (PRL) secretion is inhibited by hypothalamic dopamine. Kisspeptin controls luteinising hormone (LH) secretion and is also involved in PRL regulation. We further investigated the effect of kisspeptin-10 (Kp-10) on the activity of tuberoinfundibular dopaminergic (TIDA) neurones and the role of oestradiol (E2 ) in this mechanism. Female and male rats were injected with i.c.v. Kp-10 and evaluated for PRL release and the activity of dopamine terminals in the median eminence (ME) and neurointermediate lobe of the pituitary (NIL). Kp-10 at the doses of 0.6 and 3nmol increased plasma PRL and decreased 4-dihydroxyphenylacetic acid (DOPAC) levels in the ME and NIL of ovariectomised (OVX), E2 -treated rats but had no effect in OVX. In gonad-intact males, 3nmol Kp-10 increased PRL secretion and decreased DOPAC levels in the ME but not in the NIL. Castrated males treated with either testosterone or E2 also displayed increased PRL secretion and reduced ME DOPAC in response to Kp-10, whereas castrated rats receiving oil or dihydrotestosterone were unresponsive. By contrast, the LH response to Kp-10 was not E2 -dependent in either females or males. Additionally, immunohistochemical double-labelling demonstrated that TIDA neurones of male rats contain oestrogen receptor (ER)-α, with a higher proportion of neurones expressing ERα than in dioestrous females. The dopaminergic neurones of periventricular hypothalamic nucleus displayed much lower ERα expression. Thus, TIDA neurones express ERα in male and female rats, and kisspeptin increases PRL secretion through inhibition of TIDA neurones in an E2 -dependent manner in both sexes. These findings provide new evidence about the role of kisspeptin in the regulation of dopamine and PRL.

Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (<8 years) were included in the study. All patients underwent bone age assessment. Basal levels of serum follicle stimulating hormone and luteinizing hormone were measured and gonadotropin releasing hormone stimulation test was performed. Patients with a bone age/chronological age ratio >1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche.

A Case with Empty Sella Syndrome Combined with Multiple Anterior Pituitary Hormone Deficiencies Presenting as Hypoglycemic Coma

&lt;title&gt;Abstract A 55-year-old male was admitted to emergency department with a hypoglycemic shock of unknown origin. He was presented with tonic seizure activity after admission. Initial diagnostic procedure could exclude diabetes mellitus, drug side effects, and exogenous insulin application. Detailed evaluation of the patient's history revealed that the patient had experienced repeated hypoglycemic episodes for 2 years. He was diagnosed with hypothyroidism six years ago. Initial laboratory investigations revealed hypoglycemia, hyponatremia, and low plasma cortisol level (0.18 pg/dᄂ)· Sellar magnetic resonance imaging showed empty sella. Replacement therapy with hydrocortisone resulted in the improvement of clinical symptoms. Combined pituitary stimulation test with exception of hypoglycemia induced growth hormone and cortisol stimulation test was performed. The response of thyroid stimulating hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone was normal. We report the case of empty sella syndrome associated with hypoglycemic shock due to with multiple anterior pituitary hormone deficiencies.&lt;/p&gt;

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women.

The reproducibility of luteinizing hormone surges following agonist trigger: analysis of 1792 agonist triggers

GnRH agonist trigger is frequently used to reduce OHSS risk in high responders on antagonist protocols. It has been reported that oocyte quality is related to the pituitary response of luteinizing hormone (LH) “surge”. We examine the reproducibility of LH surges in repeated cycles in the same subjects.

Distinct roles of age and abdominal visceral fat in reducing androgen receptor-dependent negative feedback on LH secretion in healthy men.

Testosterone (T) impacts luteinizing hormone (LH) secretion through negative feedback via the androgen receptor (AR) in the hypothalamo-pituitary system. An untested postulate is that increasing body mass index (BMI), abdominal visceral fat (AVF) or total abdominal fat (TAF) with ageing decreases LH secretion by heightening T negative feedback via AR. This hypothesis was tested in a prospective, randomized double-blind cross-over study of 19 healthy men comparing the effects of flutamide, a selective non-steroidal AR antagonist and placebo administration on basal and pulsatile LH secretion as a function of age and obesity measures. To this end, serum levels of 2-hydroxyflutamide (2-OHF), a major active flutamide metabolite, were measured by mass spectrometry, and AVF/TAF quantified by abdominal computerized tomography. Statistical analysis showed that antiandrogen administration elevated 6-h mean LH concentrations to 5.4 ± 1.3 IU/L compared with 3.3 ± 1.2 IU/L for placebo (p < 10(-3) ), and total T by 35% (p < 10(-4) ). The LH-T concentration product doubled (p < 10(-8) ). According to deconvolution analysis, flutamide exposure increased total LH secretion (p < 10(-3) ) and pulsatile LH secretion (p = 0.0077), along with LH pulse frequency (p = 0.019). Despite feedback inhibition, the LH-T product declined as a linear function of AVF (p = 0.021) and TAF (p = 0.017). This was explained by the fact that higher BMI was associated with lower 2-OHF concentrations (R = -0.562, p = 0.012). In contrast, age was associated with less pulsatile LH secretion (R = -0.567, p = 0.011) even when LH responses were normalized to antiantrogen levels. In conclusion, increased AVF, TAF and BMI predict decreased LH and flutamide blood levels, whereas older age is marked by impaired stimulation of pulsatile LH secretion even when normalized for antiandrogen levels, suggesting different mechanisms of regulation by adiposity and age.

Myo‐inositol modulates insulin and luteinizing hormone secretion in normal weight patients with polycystic ovary syndrome

To investigate hormonal dynamics in a group of non-obese polycystic ovary syndrome (PCOS) patients under myo-inositol (MYO) administration. Hormonal profiles, insulin response to oral glucose tolerance test (OGTT) and luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation test before and after the administration of a preparation of MYO (3 g p.o. daily) mixed with lactoferrin and bromelin, in a group (n = 24) of normal weight PCOS patients. After the treatment interval, body mass index (BMI) did not change while LH, LH/follicle-stimulating hormone, 17-hydroxy-progesterone and androstenedione decreased significantly. Insulin response to OGTT was significantly reduced after the treatment interval (P < 0.05) as well as GnRH-induced LH response (P < 0.05). High-sensitivity C-reactive protein decreased significantly after the treatment interval. MYO administration positively modulates insulin sensitivity in non-obese PCOS patients without compensatory hyperinsulinemia, improving hormonal parameters. The presence of bromelin in the formulation modulated the pro-inflammatory state that characterizes PCOS, independently of BMI.

Recent advances in the use of an estradiol-dopamine antagonist protocol to induce ovulation in seasonally anovulatory mares

The January 1 birthday imposed by major breed registries is in conflict with the natural breeding season of the mare. Without intervention, breeders are denied the documented advantages in price and performance of foals born earlier in the year [1]. Dopamine antagonists have been used to induce early ovulation in anovulatory mares [2,3,4,5]. Kelley and associates [6] were the first to report the enhancement of prolactin secretion and superior advancement of first ovulation by pretreatment with estradiol benzoate prior to the administration of dopamine antagonist. The protocol described by Kelley et al. (6) was streamlined by Thompson et al. [7], who found that a single injection of estradiol cypionate (ECP) gave consistent prolactin and luteinizing hormone responses equivalent to those observed by Kelley et al. [6]. Subsequently, it was shown that a single injection of ECP followed by a single injection of the dopamine antagonist domperidone advanced first ovulation in anovulatorymares inwinter [8], although with a lower success rate than the earlier, more complicated protocols. The experiments described herein were conducted to assess potential improvements in the ECP-dopamine antagonist protocol for inducing ovulation in seasonally anovulatory mares.

Evaluation of the hypothalamic‐pituitary‐gonadal axis in eugonadal men with type 2 diabetes mellitus

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10min for 4h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90min after 100μg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72h post 5000IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1±25.5 vs. 99.1±13.6mg/dL, p=0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8±0.8 vs. 1.5±0.5 pulses, p=0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p=0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.

A Population of Kisspeptin/Neurokinin B Neurons in the Arcuate Nucleus May Be the Central Target of the Male Effect Phenomenon in Goats

Exposure of females to a male pheromone accelerates pulsatile gonadotropin-releasing hormone (GnRH) secretion in goats. Recent evidence has suggested that neurons in the arcuate nucleus (ARC) containing kisspeptin and neurokinin B (NKB) play a pivotal role in the control of GnRH secretion. Therefore, we hypothesized that these neurons may be the central target of the male pheromone. To test this hypothesis, we examined whether NKB signaling is involved in the pheromone action, and whether ARC kisspeptin/NKB neurons receive input from the medial nucleus of the amygdala (MeA)—the nucleus suggested to relay pheromone signals. Ovariectomized goats were implanted with a recording electrode aimed at a population of ARC kisspeptin/NKB neurons, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA) volleys, was measured. Pheromone exposure induced an MUA volley and luteinizing hormone (LH) pulse in control animals, whereas the MUA and LH responses to the pheromone were completely suppressed by the treatment with an NKB receptor antagonist. These results indicate that NKB signaling is a prerequisite for pheromone action. In ovariectomized goats, an anterograde tracer was injected into the MeA, and possible connections between the MeA and ARC kisspeptin/NKB neurons were examined. Histochemical observations demonstrated that a subset of ARC kisspeptin/NKB neurons receive efferent projections from the MeA. These results suggest that the male pheromone signal is conveyed via the MeA to ARC kisspeptin neurons, wherein the signal stimulates GnRH pulse generator activity through an NKB signaling-mediated mechanism in goats.

Mutational analysis of KISS1 and KISS1R in idiopathic central precocious puberty

The genetic background of idiopathic central precocious puberty (ICPP) is not well understood. The genetic activation of pubertal onset is thought to arise from the effect of multiple genes. Familial ICPP has been reported suggesting the existence of monogenic causes of ICPP. Kisspeptin and its receptor are found to be involved in gonadotropin-releasing hormone (GnRH) secretion and puberty onset. Mutations in their genes, KISS1 and KISSR, have been suggested to be causative for ICPP. ICPP was defined by pubertal onset before 8 years of age in girls, and a pubertal luteinizing hormone (LH) response to GnRH testing. Twenty-eight girls with ICPP were included in the study [age at diagnosis was 5.72±2.59, with a mean bone age advancement of 1.4 years (-0.1 to 2.8). Height at onset of therapy in SD score was 0.90±1.48 for age]. Luteinizing hormone-releasing hormone test was performed in all subjects, and all of them had a pubertal response (LH 20.35±32.37 mIU/mL; FSH 23.32±15.72 mIU/mL). The coding regions of KISS1 and KISS1R were sequenced. No rare variants were detected in KISS1 or KISS1R in the 28 subjects with ICPP. We confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.

Characterizing the neuroendocrine and ovarian defects of androgen receptor-knockout female mice

Homozygous androgen receptor (AR)-knockout (ARKO) female mice are subfertile due to both intra- and extraovarian (neuroendocrine) defects as defined by ovary transplantation. Using ARKO mice, this study set out to reveal the precise AR-regulated pathways required for optimal androgen-regulated ovulation and fertility. ARKO females exhibit deficient neuroendocrine negative feedback, with a reduced serum luteinizing hormone (LH) response to ovariectomy (OVX) (P < 0.01). Positive feedback is also altered as intact ARKO females, at late proestrus, exhibit an often mistimed endogenous ovulatory LH surge. Furthermore, at late proestrus, intact ARKO females display diminished preovulatory serum estradiol (E2; P < 0.01) and LH (P < 0.05) surge levels and reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus (P < 0.01) compared with controls. However, this reduced ovulatory LH response in intact ARKO females can be rescued by OVX and E2 priming or treatment with endogenous GnRH. These findings reveal that AR regulates the negative feedback response to E2, E2-positive feedback is compromised in ARKO mice, and AR-regulated negative and positive steroidal feedback pathways impact on intrahypothalamic control of the kisspeptin/GnRH/LH cascade. In addition, intraovarian AR-regulated pathways controlling antral to preovulatory follicle dynamics are disrupted because adult ARKO ovaries collected at proestrus have small antral follicles with reduced oocyte/follicle diameter ratios (P < 0.01) and increased proportions of unhealthy large antral follicles (P < 0.05) compared with controls. As a consequence of aberrant follicular growth patterns, proestrus ARKO ovaries also exhibit fewer preovulatory follicle (P < 0.05) and corpora lutea numbers (P < 0.01). However, embryo development to the blastocyst stage is unchanged in ARKO females, and hence, the subfertility is a consequence of reduced ovulations and not altered embryo quality. These findings reveal that the AR has a functional role in neuroendocrine regulation and timing of the ovulatory LH surge as well as antral/preovulatory follicle development.

Differential modulation of ghrelin-induced GH and LH release by PACAP and dopamine in goldfish pituitary cells

Ghrelin (GRLN) participates in multiple physiological processes, including the regulation of growth hormone (GH) and luteinizing hormone (LH) release. In the goldfish, neuroendocrine control of GH and LH release are multifactorial. In this system, pituitary adenylate cyclase-activating polypeptide (PACAP)-stimulated GH and LH secretion, as well as dopamine (DA)-induced GH release, are mediated by protein kinase A (PKA)-dependent, but protein kinase C (PKC)-independent, mechanisms. In addition, DA inhibits LH secretion by actions at sites along both PKA and PKC signaling pathways. Recently, goldfish GRLN (gGRLN19) has been shown to induce GH release via PKC, and LH secretion via both PKC and PKA. To further understand the neuroendocrine regulation of goldfish GH and LH release, we examined the effects of DA and PACAP on gGRLN19 actions in primary cultures of goldfish pituitary cells in perifusion and in Ca2+-imaging experiments. Consistent with their known intracellular signaling mechanisms in gonadotrophs, DA inhibited gGRLN19-induced LH release while cotreatment of PACAP and gGRLN19 did not produce additive LH responses. When applied prior to gGRLN19, PACAP potentiated gGRLN19-induced GH release and Ca2+ signals within somatotrophs. In contrast, neither prior treatment with DA followed by gGRLN19 nor pretreatment with gGRLN19 prior to PACAP produced an enhanced GH release response. These observations suggest that PKA activators positively modulate gGRLN19 actions on goldfish somatotrophs in a ligand- and treatment order-specific manner. Results add to our understanding of the complexity of neuroendocrine control of GH and LH release at the pituitary cell level, and our understanding of GRLN action.

Dietary lipid and cholesterol induce ovarian dysfunction and abnormal LH response to stimulation in rabbits.

Background/AimExcess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet) from 10 weeks of age (i.e., 2 weeks before normal onset of puberty) or a control diet (C diet).Methodology/Principal FindingsThree experiments were performed, each including 8 treated (HH group) and 8 control (C group) does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH) was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age). In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH) response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR).ConclusionThe HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR.

Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 μg GnRH challenge was tested every three months. Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

A case of natural queen succession in a captive colony of naked mole-rats, Heterocephalus glaber

Naked mole-rats occur in large colonies where usually a single queen monopolizes reproduction. Queen succession occurs from within usually as a result of aggressive encounters with subordinate females that queue for reproductive succession following colony instability, which inevitably results in death of either the queen or the challenging conspecific. We monitored a queen succession following the death of the breeding male in a colony of the naked mole-rat, Heterocephalus glaber, prior to, during as well as after replacement of the original breeding female. The response of the pituitary luteotrophs was investigated in the non-reproductive females during this period of instability by the administration of endogenous gonadotrophin releasing hormone (GnRH) and evaluating the subsequent luteinising hormone (LH) response in the blood. Larger and older non-breeding females engaged in aggressive encounters that culminated in death. The new breeding successor which arose from within the colony was a large female who continued to procreate. The six non-breeding females that were killed during reproductive takeover were larger and older females which exhibited elevated basal circulating LH concentrations as well as increased pituitary sensitivity as measured by the amount of releasable LH to an exogenous GnRH challenge. By contrast, non-breeding females that survived the succession were smaller and younger animals with reduced basal and GnRH challenged LH concentrations. Likewise, five non-breeding males which were heavier and older than those non-breeding males which survived were killed. These animals did not, however, show elevated basal or exogenous GnRH challenged LH concentrations when compared to the surviving males. The non-breeding animals of both sexes which survived the reproductive takeover event represented individuals which posed a minimal threat to the new successor and hence promoted the continuation of the marked reproductive skew that is prevalent in this highly inbred colonial subterranean hystricomorph.