Hypothalamic Ovarian Axis Research Articles

Heavy Menstrual Bleeding in the Adolescent

Heavy menstrual bleeding is a common presenting problem in the adolescent population. The average age of menarche is between 12 and 13 years. The most common reason for heavy menstrual bleeding soon after menarche is from an immature hypothalamic ovarian access, which spontaneously resolves once cycles become ovulatory. However, the broad differential diagnosis for heavy menses in adolescents includes coagulopathy, thyroid disease, sexually transmitted infections, specifically chlamydia, and chronic medical conditions. Von Willebrand disease is the most common bleeding disorder that can present with heavy menstrual bleeding at menarche or shortly after. A thorough history and physical exam with occasional labs needs to be completed and can assist in narrowing the differential diagnosis. Treatment of heavy menstrual bleeding consists of hormonal and nonhormonal options: combination oral contraceptive pills, patches, or rings taken continuously or cyclically; progesterone-only pills; progesterone implants; progesterone intrauterine devices; cyclic tranexamic acid; cyclic aminocaproic acid; and GnRH agonists with add-back therapy. This review contains 3 tables, and 28 references. Key Words: adolescent menses, anovulation, bleeding disorder, heavy menstrual bleeding, immature hypothalamic ovarian axis, menarche, treatment of heavy menses, Von Willebrand disease

JMJD3 Is Crucial for the Female AVPV RIP-Cre Neuron-Controlled Kisspeptin–Estrogen Feedback Loop and Reproductive Function

The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. Although most studies have focused on the hierarchy from the brain to the gonad, many questions remain unresolved concerning the feedback from the gonad to the central nervous system, especially regarding the potential epigenetic modifications in hypothalamic neurons. In the present report, we generated genetically modified mice lacking histone H3 lysine 27 (H3K27) demethylase Jumonji domain-containing 3 (JMJD3) in hypothalamic rat-insulin-promoter-expressing neurons (RIP-Cre neurons). The female mutant mice displayed late-onset obesity owing to reduced locomotor activity and decreased energy expenditure. JMJD3 deficiency in RIP-Cre neurons also results in delayed pubertal onset, an irregular estrous cycle, impaired fertility, and accelerated ovarian failure in female mice owing to the dysregulation of the hypothalamic-ovarian axis. We found that JMJD3 directly regulates Kiss1 gene expression by binding to the Kiss1 promoter and triggering H3K27me3 demethylation in the anteroventral periventricular (AVPV) nucleus. Further study confirmed that the aberrations arose from impaired kisspeptin signaling in the hypothalamic AVPV nucleus and subsequent estrogen deficiency. Estrogen replacement therapy can reverse obesity in mutant mice. Moreover, we demonstrated that Jmjd3 is an estrogen target gene in the hypothalamus. These results provide direct genetic and molecular evidence that JMJD3 is a key mediator for the kisspeptin-estrogen feedback loop.

La administración de tungstato sódico restaura la ovulación y la fertilidad en ratones infértiles IRS2−/−

Insulin receptor substrate-2 (IRS-2) gene suppression induces an alteration of hypothalamic-ovarian axis as a result of central leptin resistance induction. IRS-2−/−females mice are characterised by persistent anovulation, accompanied by the absence of the oestrous cycle, which results in a marked reduction in fertility (pregnancy rate: 9% IRS-2−/−vs. 100% IRS-2wt). Sodium tungstate (Na2WO4) has demonstrated its ability to reverse the leptin resistance state through an inhibition of phosphatases involved in the signalling pathway of several cytokines. The objective of this work is to present an experimental approach to determine a potential interest towards Na2WO4 in the reproductive ability of anovulatory IRS-2−/− female mice. Material and methodsNa2WO4 was administered in drinking water (2g/L) to female mice. The oestrous cycle was assessed through vaginal smears, and pregnancy rates were measured after mating with IRS-2wt males. ResultsLack of oestrous cycle was confirmed in the mice during the pre-treatment period. After 7 days of treatment all animals showed delayed cycle phases (oestrous and meta-oestrous) in vaginal smears, indicating a recovery of normal ovulatory cycle. At the end of the study, after mating with competent IRS-2wt male, 80% of females treated with Na2WO4 were pregnant. These results show a fertility recovery, as opposed to the pregnancy rate described in untreated IRS-2−/− (9%). ConclusionsFor the first time, a description is presented of the direct effect of Na2WO4 in the restoration of ovarian function and fertility in IRS-2−/− female mice.

Serum anti-Müllerian hormone, inhibin B, and total inhibin levels in women with hypothalamic amenorrhea and anorexia nervosa

Objective. To evaluate whether neuroendocrine forms of secondary amenorrhea (hypothalamic nervosa (HA) and anorexia nervosa (AN)) affect serum anti-Müllerian hormone (AMH), inhibin B, and total inhibin levels.Methods. Amenorrheic women (n = 82) (aged between 16 and 35 years old) according to diagnosed with neuroendocrine forms of amenorrhea: HA (n = 64), AN (n = 18), and healthy women (n = 41) (control group) were enrolled. Serum AMH, inhibin B, and total inhibin levels were measured by specific ELISA.Results. No statistically significant difference of AMH serum levels between women with HA, AN, and control group was observed. Serum inhibin B and total inhibin levels in women with HA (p < 0.0001), AN (p < 0.05) resulted significantly lower than in control healthy women.Conclusion. The present data showed that neuroendocrine forms of amenorrhea are associated with an impaired inhibin secretion while not AMH. These data indirectly support that AMH is an excellent marker of ovarian reserve and its secretion is not influenced by the hypothalamic-ovarian axis activity.

Abnormal bleeding in adolescents.

Abnormal bleeding is a common clinical problem in adolescents, with the vast majority of cases resulting from anovulatory menstrual cycles. Although most episodes of abnormal vaginal bleeding do not cause acute medical complications, bleeding can be traumatic for young patients and their families. Health care providers with a solid knowledge of menstrual physiology and a thorough approach to differential diagnosis can evaluate and appropriately manage adolescents. In this article, we review the maturation of the hypothalamic ovarian axis, the most frequent etiologies of abnormal bleeding, as well as other less common causes and discuss diagnosis and treatment modalities.

Nitromusk Compounds in Women with Gynecological and Endocrine Dysfunction

Musk xylene (MX), musk ketone (MK), musk ambrette, musk moskene, and musk tibetene are synthetic fragrances. Between 1994 and 1996 these five nitromusk compounds (NMCs) were tested in the blood of 152 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. The testing was conducted by gas chromotography with mass-specific detector and mass spectrometry in a retrospective cross-sectional study. MX was detected in 95% and MK in 85% of the blood samples (>20 ng per liter whole blood). The median concentration of MX was 65.5 ng/L and the maximum level of MX was 1183 ng/L; the corresponding values for MK were respectively 55.5 and 518 ng/L. The other three NMCs were found in only a few patients or not at all. Significant associations between MX and MK concentrations were found in blood and different clinical parameters of the endocrine system. MX and MK may act centrally as a disrupter of the (supra-) hypothalamic–ovarian axis, which may result in a mild ovarian insufficiency. On the basis of our data, a reproductive toxicity and an endocrine effect of NMCs in women cannot be ruled out. Further experimental and clinical studies should be conducted.

Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: relationship to the reproductive cycle.

The relationship between diabetes and the morphological alterations which occur in hypothalamic and ovarian tissue was examined in the long-term, ketonuric-diabetic Chinese hamster. Matched diabetic and non-diabetic control hamsters were inspected daily for changes in the reproductive cycle by vaginal lavage. On dioestrus, animals were perfused, the hypothalamus and ovaries collected, prepared for microscopy and morphometrically analyzed. The nuclei in the medial basal hypothalamus of diabetic hamsters exhibited a decreased area (p less than 0.01) and neuronal population (p less than 0.05-0.01) compared with controls. The ovaries of the diabetic animals had a reduced follicular population (p less than or equal to 0.05) and an increased atresia rate (p less than or equal to 0.05) compared with controls. In addition, all diabetic hamsters were acyclic. In diabetic animals, the corpora luteal cells contained a reduced lipid content (p less than or equal to 0.001) which was possibly functionally related to a significant decline in serum progesterone levels (p less than or equal to 0.01). Based on these results it is suggested that the hypothalamic-ovarian axis is both morphologically and functionally impaired in the diabetic hamster.

Effect of glucose on hypothalamic feeding centers in deafferented animals.

ARTICLESEffect of glucose on hypothalamic feeding centers in deafferented animalsGS Chhina, BK Anand, B Singh, and PS RaoGS Chhina, BK Anand, B Singh, and PS RaoPublished Online:01 Aug 1971https://doi.org/10.1152/ajplegacy.1971.221.2.662MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Download PDF FiguresReferencesRelatedInformation Cited ByFunctional MRI of human hypothalamic responses following glucose ingestionNeuroImage, Vol. 24, No. 2The lateral hypothalamic area revisited: Ingestive behaviorNeuroscience & Biobehavioral Reviews, Vol. 20, No. 2Developmental and regional changes in brain norepinephrine levels in diabetic C57BL/KsJ mice: effects of estradiol and progesteroneDevelopmental Brain Research, Vol. 89, No. 2Age- and diabetes-associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ miceDevelopmental Brain Research, Vol. 51, No. 2Caudal Brainstem Participates in the Distributed Neural Control of FeedingMorphometric analysis of obesity (ob/ob)- and diabetes (db/db)-associated hypothalamic neuronal degeneration in C57BL/KsJ miceBrain Research, Vol. 501, No. 1Central Nervous System Control of Nutrient Homeostasis1 January 2011Caudal Brainstem Integration of Taste and Internal State Factors in Behavioral and Autonomic ResponsesCAUDAL BRAINSTEM CONTRIBUTIONS TO THE INTEGRATED NEURAL CONTROL OF ENERGY HOMEOSTASISFourth ventricular phlorizin dissociates feeding from hyperglycemia in ratsBrain Research, Vol. 341, No. 2Morphometric analysis of medial basal hypothalamic neuronal degeneration in diabetes (db/db) mutant C57BL/KsJ mice: Relation to age and hyperglycemiaDevelopmental Brain Research, Vol. 20, No. 2Glucose utilization by the mouse brain: Influence of age and diabetesDevelopmental Brain Research, Vol. 15, No. 2Diabetes-associated, ventromedial hypothalamic neuronal degeneration in the Chinese hamsterNeuroscience Letters, Vol. 44, No. 3Two types of medial hypothalamic inhibition of lateral hypothalamic rewardBrain Research, Vol. 277, No. 2Diabetes-associated hypothalamic neuronal depopulation in the aging Chinese hamsterDevelopmental Brain Research, Vol. 9, No. 3Insulin Elicits Ingestion in Decerebrate RatsScience, Vol. 221, No. 4606Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: Relationship to the reproductive cycleDiabetologia, Vol. 23, No. 3Depopulation of the ventromedial hypothalamic nucleus in the diabetic Chinese hamsterActa Neuropathologica, Vol. 56, No. 1Current evidence for a role of glucose as a regulator of hypothalamic function and caloric homeostasisPsychoneuroendocrinology, Vol. 6, No. 4Reflex insulin secretion due to central hyperglycemia promoted by intracarotid glucose infusion in dogsPhysiology & Behavior, Vol. 23, No. 2The Forebrain Is Not Essential for Sympathoadrenal Hyperglycemic Response to GlucoprivationScience, Vol. 204, No. 4397Huntington’s Disease: Premature Brain Aging with Abnormalities of Chemical Neurotransmitters and Hormonal FunctionIncreased feeding in response to bilateral injection of insulin antibodies in the VMHPhysiology & Behavior, Vol. 19, No. 2Noradrenergic feeding system in monkey hypothalamus is altered by localized perfusion of glucose, insulin, 2-DG and eatingPharmacology Biochemistry and Behavior, Vol. 5, No. 4Effects of insulin injection on responses of olfactory bulb and amygdala single units to odorsBrain Research, Vol. 99, No. 1Effects of glucose on multiple-unit activity of the hypothalamus in female ratsExperimental Neurology, Vol. 49, No. 2Hyperglycemia and inhibition of insulin secretion by 2-deoxy-d-glucose in rats with hypothalamic lesionsPharmacological Research Communications, Vol. 7, No. 2Effect of hypoglycemia induced by insulin on the depth EEG in the chickenGeneral and Comparative Endocrinology, Vol. 23, No. 2Biogenic Amines in the Hypothalamus: Effect of L-DOPA on Human Growth Hormone Levels in Patients with Huntington's ChoreaINCREASED FREQUENCY OF DIABETES MELLITUS IN PATIENTS WITH HUNTINGTON'S CHOREAThe Lancet, Vol. 299, No. 7765 More from this issue > Volume 221Issue 2August 1971Pages 662-667 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.221.2.662PubMed4934668History Published online 1 August 1971 Published in print 1 August 1971 Metrics