Hypothalamic-pituitary Axis Function Research Articles

Microsurgical Management of Complex Hypothalamic Hamartomas in the Era of Minimally Invasive Therapy: A Case Series and Narrative Review

There has been a paradigm shift in the management of hypothalamic hamartoma (HH) from traditional microsurgical techniques to less invasive alternatives. However, large and extensive HH may fail to respond to these therapies, necessitating craniotomies. All patients who underwent microsurgical resection of a complex HH by the 2 senior authors from 2011 to 2021 were included. Charts were retrospectively reviewed and demographic, clinical, imaging, and outcome data were recorded. Eight patients (mean age, 7 years) were included. Two had failed previous treatments. All 7 presented with gelastic seizures and cognitive dysfunction, 6 showed central precocious puberty, and 3 had behavioral problems. The mean lesion size was 21.6 mm and all had interpeduncular extension, 5 had intraventricular extension (Delalande type I, 3; type III, 4; type IV, 1). A frontotemporal orbitozygomatic approach with optic nerve decompression was used in all patients, supplemented by another approach in 3 (endoscopic transventricular, 3; transcallosal, 1). Gross total resection was achieved in 6 patients and subtotal resection in 2. Transient complications occurred in 3 patients (37.5%): self-limited sodium imbalance (n= 3), subdural hygroma (n= 2). Permanent complications occurred in 2 patients (25%): perforator infarct (n= 1) and short-term memory loss (n= 1). All patients experienced seizure resolution with preserved hypothalamic-pituitary axis function. After a mean follow-up of 41 months (range, 2-66 months), 7 patients remained seizure free, and 1 had rare seizures. Cognitive and behavioral symptoms improved in all patients. For large HH with interpeduncular extension, microsurgery via the frontotemporal orbitozygomatic approach is a safe and highly effective treatment modality.

The Interplay Between Pituitary Health and Diabetes Mellitus - The Need for 'Hypophyseo-Vigilance'.

The anterior and posterior hypophyseal hormones alter glucose metabolism in health and disease. Secondary diabetes may occur due to hypersecretion of anterior pituitary hormones like adrenocorticotrophic hormone in Cushing's disease and growth hormone in acromegaly. Other hormones like prolactin, gonadotropins, oxytocin and vasopressin, though not overtly associated with causation of diabetes, have important physiological role in maintaining glucose homeostasis. Hypoglycaemia is not an unusual occurrence in hypopituitarism. Many of the medications that are used for treatment of hypophyseal diseases alter glucose metabolism. Agents like pasireotide should be used with caution in the setting of diabetes, whereas pegvisomant should be given preference. Diabetes mellitus itself, on the other hand, can alter the functioning of hypothalamic pituitary axis; this is documented in both type 1 and type 2 diabetes. This review focuses on the clinically relevant interplay of hypophyseal hormones and glucose homeostasis. The authors define 'hypophyseo-vigilance' as an approach which keeps the bidirectional, multifaceted interactions between the pituitary and glucose metabolism in mind while managing diabetes and pituitary disease.

Postoperative day 1 versus postoperative day 5 morning cortisol for predicting an intact hypothalamic-pituitary axis: A cohort analysis

Background:A reliable standard for evaluating postoperative hypothalamic-pituitary-axis (HPA) function following transsphenoidal pituitary surgery (TSS) could reduce hospital stays and unnecessary prolonged steroid therapy. We retrospectively examined the predictive role of morning cortisol levels on long-term HPA function to develop an institutional protocol. Here, we report the results of this analysis, which is the first to report the predictive strength of multiple variables (i.e., timing of measurement and values of serum cortisol cutoffs) within the same cohort.Methods:A retrospective chart review was performed in 183 patients at a single institution from 2007 to 2012. 67 patients met inclusion criteria. The predictive value of postoperative day (POD) 1 and POD 5 morning cortisol for HPA function as determined by 1 ug cosyntropin stimulation test was evaluated using standard confusion matrix calculations and receiver-operator control curve analysis.Results:In our cohort, an early POD 5 serum morning cortisol ≥15 ug/dl predicted an intact HPA axis with 100% specificity, 51% sensitivity, and a positive predictive value (PPV) of 100%. A POD 1 serum cortisol ≥25 ug/dl was needed to achieve a specificity of 100% and PPV of 100% to predict an intact HPA axis with a sensitivity of 30%. A POD 1 serum cortisol ≥18 ug/dl predicted an intact HPA axis with 33.3% specificity, PPV of 90.9%, and a sensitivity of 51.3%.Conclusion:A POD 5 morning cortisol level ≥15 ug/dl is an excellent predictor of normal postoperative HPA function in patients undergoing TSS for pituitary adenoma.

Improvement of Pituitary Function after Carotid Revascularization in Patients with Abnormal Cerebral Perfusion - A Pilot Study.

Brain ischemia may affect hypothalamic-pituitary axis function, which may influence the outcomes of patients with internal carotid artery (ICA) stenosis/occlusion. The objective of this study was to determine the influence of successful carotid revascularization on pituitary function in patients with severe ICA stenosis/occlusion. This study was conducted from April 2009 to December 2014. Patients receiving successful endovascular interventions for severe ICA stenosis/occlusion were enrolled. The patients were divided into 2 groups: group 1 with abnormal ipsilateral cerebral perfusion, and group 2 without. Endocrine profiles were measured before and > 1 year after the procedure. Computed tomography perfusion studies were used to assess brain perfusion. Thirty-seven patients received successful interventions. Three patients were excluded due to re-stenosis before 1 year. There were 23 and 11 patients in group 1 and 2, with mean ages of 68 and 69 years, respectively. In the female patients, follicular stimulating hormone (FSH) and luteinizing hormone (LH) increased significantly (p = 0.043) after the interventions with a stable estradiol level in group 1. In contrast, FSH, LH and estradiol showed a decreasing trend in group 2. In the male patients, FSH and LH increased significantly (p < 0.01) after the interventions with a stable testosterone level in group 1, while testosterone showed a decreasing trend in group 2. Thyroid stimulating hormone increased significantly in the women in both groups, and in the men in group 1. Successful revascularization for severe ICA stenosis/occlusion may improve their pituitary function, especially FSH and LH levels.

Long-term consequences of obesity on female fertility and the health of the offspring.

Obesity has reached near epidemic levels among reproductive age women with a myriad of consequences. Obesity adversely affects the maternal milieu by creating conditions that decrease fertility and increase the risk of gestational diabetes, hypertensive disease in pregnancy, fetal growth abnormalities and congenital anomalies. The effects of obesity are not limited to pregnancy. Indeed, beyond the immediate postpartum period, obese women maintain a higher prevalence of insulin resistance and cardiovascular disease. In this article, we will review the pathophysiology underlying the effects of obesity on fertility, pregnancy outcome and health status of offspring. The purpose of this review is to outline proposed models responsible for the short-term and long-term consequences of obesity on fertility and offspring development, and identify knowledge gaps where additional research is needed. Maternal over or under nutrition adversely affect maternal reproductive capacity and pregnancy success. Separate from effects on maternal reproductive function, maternal over or under nutrition may also 'program' fetal pathophysiology through inheritance mechanisms that suggest epigenetic modification of DNA, differential RNA translation and protein expression, or modification of the fetal hypothalamic-pituitary axis function through programmed adverse effects on the developing hypothalamic circuitry. The concept of maternal health modifying the risk of developing noncommunicable diseases in the offspring is based on Developmental Origins of Health and Disease hypothesis. Of importance, the long-term effects of obesity are not limited to maternal health, but also programs pathophysiology in their offspring. Children of obese gravida are at increased risk for the development of cardiometabolic disease in childhood and throughout adulthood. Future studies directly interrogating mechanisms underlying the risks associated with obesity will allow us to develop interventions and therapies to decrease short-term and long-term morbidities associated with maternal obesity.

Procalcitonin and Midregional Proatrial Natriuretic Peptide as Markers of Ischemic Stroke: The Northern Manhattan Study.

Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke (IS). We hypothesized that selected blood biomarkers of infection (procalcitonin [PCT]), hypothalamic-pituitary-axis function (copeptin), and hemodynamic dysfunction (midregional proatrial natriuretic peptide [MRproANP]) are associated with incident IS risk in the multiethnic, urban Northern Manhattan Study (NOMAS) cohort. A nested case-control study was performed among initially stroke-free participants. Cases were defined as first IS (n=172). We randomly selected controls among those who did not develop an event (n=344). We calculated Cox proportional hazards models with inverse probability weighting to estimate the association of blood biomarkers with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. Those with PCT and MRproANP, but not copeptin, in the top quartile, compared with the lowest quartile, were associated with IS (for PCT adjusted hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.8 and for MRproANP adjusted HR, 3.5; 95% CI, 1.6-7.5). The associations of PCT and MRproANP differed by stroke etiology; PCT levels in the top quartile were particularly associated with small vessel stroke (adjusted HR, 5.1; 95% CI, 1.4-18.7) and MRproANP levels with cardioembolic stroke (adjusted HR, 16.3; 95% CI, 3.7-70.9). Higher levels of PCT, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with IS risk. PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk. Further study is needed to validate these biomarkers and determine their significance in stroke risk prediction and prevention.

Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions.

Background: Bisphenol-A (BPA) is widely used and ubiquitous in the environment. Animal studies indicate that BPA affects reproduction, however, the gene-environment interaction mechanism(s) involved in this association remains unclear. We performed a literature review to summarize the evidence on this topic. Methods: A comprehensive search was conducted in PubMed using as keywords BPA, gene, infertility and female reproduction. Full-text articles in both human and animals published in English prior to December 2014 were selected. Results: Evidence shows that BPA can interfere with endocrine function of hypothalamic-pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH) secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. Both epidemiological and experimental evidences demonstrate that BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational. Conclusions: Evidence on gene-environment interactions, especially from human studies, is still limited. Further research on this topic is warranted.

Reductions in cortisol associated with primary care brief mindfulness program for veterans with PTSD.

Patients with posttraumatic stress disorder (PTSD) have significant medical morbidity, which may be mediated by hypothalamic pituitary axis (HPA) dysfunction and reflected in cortisol output. Many veterans with PTSD are hesitant to engage in trauma-focused exposure treatments; therefore briefer, non-exposure-based treatments are needed; one such promising approach is an abbreviated Primary Care brief Mindfulness Program (PCbMP). This study investigated the relationship between dose-response to participation in a veterans PCbMP program and diurnal cortisol. Cortisol reflects HPA function and PTSD is associated with HPA dysregulation. Veterans with PTSD were identified in PC and randomly assigned to treatment as usual (TAU, n=21) or participation in brief 4-week Mindfulness Based Stress Reduction program (n=19). Veterans (n=40) (mean age, 48±16 y; 90% men) with PTSD referred through their VA PC provider and randomly assigned to PCbMP or TAU. As an objective indicator of HPA function, salivary diurnal cortisol was measured from samples collected across 2 consecutive days at baseline and follow-up. Analyses revealed that significant changes in cortisol were associated with PCbMP treatment engagement and dosing (number of mindfulness program sessions completed). Veterans completing 4 mindfulness-based meditation sessions significantly reduced their cortisol awakening response (P≤0.05); and had significant changes in cortisol area under the curve increase compared with TAU participants (P≤0.05). Results indicate that PCbMP has a beneficial physiological impact on veterans with PTSD with a minimum of 4 weeks of practice.

Hyperprolactinémies induites par les antipsychotiques : physiopathologie, clinique et surveillance

Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it. Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don't mention them spontaneously and clinicians underestimate their prevalence. In the long-term, hypogonadism involves a premature bone loss in men and women. Klibanski and colleagues showed that this loss is significant only in women with hyperprolactinemia associated with amenorrhea. That suggests that prolactin is not directly responsible for this clinical feature. Nevertheless, prolactin seems to be involved in the development of breast cancer, but its role is unclear for prostate cancer. Our review promotes a check-up before beginning a treatment with antipsychotic agents. First, a baseline prolactin level should be measured. It should also include the research on previous treatment with antipsychotic-drugs and the assessment of adverse effects suggestive of hyperprolactinemia. Questioning should finally look for any contra-indication to antipsychotics. Monitoring during antipsychotic treatment has been studied by a group of international experts in psychiatry, medicine, toxicology and pharmacy who made a critical review of clinical guidance on hyperprolactinemia. Experts notify that it is important to check whether patients have any sexual dysfunction, such as loss of libido or menstrual irregularity, and galactorrhoea. Prolactin level should also be controlled after three months of stable dose treatment, or if any clinical feature of hyperprolactinemia appears. If a patient prescribed antipsychotic-drugs has a confirmed prolactin level above the normal range, it is necessary to exclude other causes of hyperprolactinemia. If antipsychotics are really involved, the management should be adapted with the prolactin level and the patient him/herself. To summarize, clinicians can decrease the dose of the antipsychotic or switch to a prolactin-sparing drug. Oral contraceptives can be added whether to prevent pregnancy or to prevent bone loss and osteoporosis. Finally, experts recommend reserving dopamine agonists to treat antipsychotic-induced hyperprolactinemia in very exceptional circumstances as it can worsen the mental illness.

As proteínas de relógios e o eixo hipotálamo-hipófise-gonadal de fêmeas de roedores

The components of hypothalamus-pituitary-gonadal axis release their products in a circadian-temporal window; this is crucial for the reproductive success in either spontaneous or inducible ovulators. The preovulatory surge of luteinizing hormone (LH) is preceded by a hypersecretion of the gonadotrophin-releasing hormone (GnRH). In rodents, it is already known that the timed, preovulatory activation of GnRH-secreting neurons depends on a complex interacting neuroendocrine mechanism involving two cyclic signals: an ovarian estradiol rise in plasma levels during the follicular phase of the estrous cycle and a neural signal from the suprachiasmatic nuclei (SCN). Evidences supporting the hypothesis that the hypothalamic-pituitary axis function depends on the integrity of an autoregulatory loop of expression of clock proteins on each of its components are increasing. This review discusses these evidences

The impact of the site of origin and rate of tumour growth on clinical outcome in children with craniopharyngiomas

Data on many predictors of hypothalamic-pituitary axis dysfunction associated with childhood craniopharyngioma (CP) are rather inconsistent, probably reflecting the variable but as yet unclarified growth pattern of these tumours. The aim of this study was to define the determinative role of tumour growth pattern on hypothalamic-pituitary axis function and outcomes for childhood CPs. The authors retrospectively analysed the records of 81 consecutive children with primary CP who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. The patients were divided into two subgroups based on tumour location and growth patterns: group A (infra-diaphragmatic sellar tumours: 34 cases) and group B [third ventricular floor (3rd VF) tumours: 47 cases]. The children's pre- and postsurgical endocrinological and hypothalamic disturbances were compared. Pituitary function and hypothalamic statues were quantitatively assessed using classification systems proposed in the previous studies. Preoperative pituitary function was more severely compromised in patients in group A than those in group B and deteriorated significantly following resection in both groups. (Average pituitary function scores increased from 2·19 ± 0·83 to 3·31 ± 0·74, P < 0·001). At the last follow-up, children with 3rd VF tumours had more prevalent weight gain (median body mass index: 23·1 kg/m(2) in group B vs 19·7 kg/m(2) in group A, P < 0·001) and increased hypothalamic dysfunction (average hypothalamic status scores: 2·04 ± 0·97 in group B vs 1·29 ± 0·57 in group A, P < 0·001). Children with 3rd VF tumours had a significantly lower probability of recurrence-free survival than those with sellar tumours (at 5 years: 74%vs 49%, respectively; at 10 years: 66%vs 32%, respectively; P = 0·02). Substantial differences in the outcome of childhood CP with different tumour growth patterns and locations were found, which suggested that diverse therapeutic considerations, especially endocrinological substitution, might be emphasized.

Altered Brain Activation During Visuomotor Integration in Chronic Active Cannabis Users: Relationship to Cortisol Levels

Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. Thirty cannabis users (16 men, 14 women, 18-45 years old) and 30 nondrug user controls (16 men, 14 women, 19-44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and with fMRI using a 3 Tesla scanner during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. The greater but altered brain activities may be mediated by the higher cortisol levels in the cannabis users, which in turn may lead to less efficient visual-motor function.

Radiation-induced hypopituitarism after cancer therapy: who, how and when to test

Subtle to frank abnormalities in hypothalamic-pituitary axis function are frequently seen in cancer survivors who have received prophylactic or therapeutic cranial irradiation. The growth hormone (GH) axis is the most vulnerable to radiation damage, and isolated GH deficiency can occur after doses as low as 18 Gy. Furthermore, the frequency of GH deficiency can reach 50-100% within 3-5 years of cranial irradiation with doses of 30-50 Gy. TSH and adrenocorticotropic hormone deficiency occur in 3-6% of patients after conventional irradiation (30-50 Gy). Abnormalities in gonadotropin secretion are dose-dependent: gonadotropin deficiency is seen only after doses of 30 Gy or more, whereas lower doses usually lead to precocious puberty. Hyperprolactinemia predominantly occurs in young women after intensive irradiation and is usually subclinical. The frequencies of gonadotropin, adrenocorticotropic hormone and TSH deficiencies substantially increase with intensive irradiation (greater than 60 Gy) and after conventional irradiation for pituitary tumors, with a cumulative incidence of 30-60% after 10 years. The irreversible and progressive nature of radiation-induced anterior-pituitary hormone deficiencies and their adverse effect on body image, growth, sexual function, skeletal health and quality of life makes it essential that cancer survivors are tested regularly to ensure appropriate diagnosis and timely hormone replacement therapy.

Neurofibromin regulates somatic growth through the hypothalamic–pituitary axis

To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain development, we recently generated mice in which Nf1 gene inactivation occurs in neuroglial progenitor cells using the brain lipid binding protein (BLBP) promoter. We found that Nf1(BLBP)CKO mice exhibit significantly reduced body weights and anterior pituitary gland sizes. We further demonstrate that the small anterior pituitary size reflects loss of neurofibromin expression in the hypothalamus, leading to reduced growth hormone releasing hormone, pituitary growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production. Since neurofibromin both negatively regulates Ras activity and positively modulates cAMP levels, we examined the signaling pathway responsible for these abnormalities. While BLBP-mediated expression of an activated Ras molecule did not recapitulate the body weight and hypothalamic/pituitary defects, treatment of Nf1(BLBP)CKO mice with rolipram to increase cAMP levels resulted in a partial restoration of the body weight phenotype. Furthermore, conditional expression of the Ras regulatory GAP domain of neurofibromin also did not rescue the body weight or Igf1 mRNA defects in Nf1(BLBP)CKO mice. Collectively, these data demonstrate a critical role for neurofibromin in hypothalamic-pituitary axis function and provide further insights into the short stature and GH deficits seen in children with NF1.

Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function

Developmental vitamin D deficiency (DVD) has been shown to alter the orderly pattern of brain development. Even though the period of vitamin D deficiency is restricted to gestation this is sufficient to induce behavioural abnormalities in the adult offspring consistent with those seen in many animal models of schizophrenia. Given that some of these behavioural alterations could also be an indirect result of either impaired maternal hypothalamic pituitary axis (HPA) function (which in turn could influence maternal care) or the result of a permanent alteration in HPA function in the adult offspring we have examined HPA status in both maternal animals and adult offspring. In this study we have established that HPA function is normal in the maternally vitamin D deficient rat. We replicate the behavioural phenotype of hyperlocomotion whilst establishing that HPA function is also unchanged in the adult male offspring. We conclude that the behavioural alterations induced by DVD deficiency are due to some adverse event in brain development rather than via an alteration in stress response.

Effects of Chinese herbal medicine on modulating the course of puberty development in children with precocious puberty

To explore the therapeutic effects of Ziyin Xiehuo Recipe (ZYXHR) for nourishing yin and lowering fire and Yishen Tianjing Recipe (YSTJR) for nourishing kidney and replenishing essence on regulating the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis, and to reveal the mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development of children with precocious puberty. The pubertal rats were fed with ZYXHR or YSTJR for 30 days, and the parameters of rats were monitored as the followings: The content of gonadotropin-releasing hormone (GnRH), the frequency and amplitude of GnRH impulse releasing, the releasing amounts of aminoacid neurotransmitters, and neuropeptide Y (NPY) and beta-endorphin (beta-END) in the gonadotrophic area of the hypothalamus were detected with neurobiological methods (push-pull perfusion, homogenate, incubation of brain slices, and immunohistochemical staining). The levels of gene and protein expressions of GnRH, growth hormone releasing hormone (GHRH) and somatostatin (SS) in hypothalamus, and follicular stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) in adenohypophysis as well as insulin-like growth factor I (IGF-I) in metaphysis were determined with real time reverse transcription-polymerase chain reaction (RT-PCR). The ZYXHR could reduce the activity of GnRH neurons in hypothalamus through inhibiting the release of central exciting aminoacid neurotransmitters, whereas promoting the release of central inhibiting aminoacid neurotransmitters, NPY and beta-END in gonadotrophic area of hypothalamus. The expression levels of GnRH, FSH and LH mRNAs were down-regulated while the expression level of SS mRNA in hypothalamus was up-regulated in the ZYXHR-treated group. The GH mRNA in hypophysis and the IGF-I mRNA in metaphysis were both down-regulated by ZYXHR. The YSTJR could promote the activity of GnRH neurons in hypothalamus through inhibiting the release of NPY in gonadotrophic area of hypothalamus, up-regulating the expression levels of GnRH, FSH, LH and GH mRNAs in hypophysis, and IGF-I mRNA in metaphysis, while down-regulating the expression level of SS mRNA in hypothalamus. The ZYXHR and YSTJR could both regulate the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis through modulating the neuroendocrine regulation and the gene expressions of GnRH and SS in hypothalamus, GH, FSH and LH in hypophysis, and IGF-I in metaphysis. These may be the chief mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development and ameliorating the skeletal development in children with precocious puberty.

Human sexuality, sex hormones, and epilepsy

The function of the hypothalamic–pituitary axis (HPA), including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone, and prolactin, and the concentrations and metabolism of its end products, such as estrogen, testosterone, and dehydroepiandrosterone, appear to be modified in many people with epilepsy. Effects of the disorder itself and effects of antiepileptic drugs (AEDs) both appear to contribute to these hormonal alterations, which may be associated with sexual dysfunction. Focal epileptic discharges from the temporal lobe may affect HPA function, as is suggested by the normalization of androgen levels seen in men with temporal lobe epilepsy who become seizure-free after surgery. Hepatic enzyme-inducing AEDs such as carbamazepine and phenytoin may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been implicated in the causation of reproductive endocrine abnormalities. Polycystic ovaries and polycystic ovarian syndrome (PCOS) are widely believed to be common in women with epilepsy, but the actual prevalence and the pathogenesis of PCOS in this population are disputed. Hormonal changes and sexual dysfunction need to be addressed in any comprehensive approach to epilepsy management, as well as any comprehensive epilepsy research program. Avoidance of enzyme-inducing AEDs and achievement of freedom from seizures as the goal of treatment are strongly recommended.

Effects of combined exposure to lead and cadmium on the hypothalamic–pituitary axis function in proestrous rats

The effects of lead and cadmium on the hypothalamic–pituitary axis were studied in proestrous rats. Adult female rats were treated intraperitonially with either lead acetate and cadmium acetate alone or in combination at a dose of 0.05 mg/kg daily for 15 days. Serotonin (5-HT) and norepinephrine (NE) levels decreased in individually and combined metal treated groups whereas dopamine (DA) levels were decreased only in the cadmium-exposed group. The pituitary levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were decreased significantly in cadmium and combined treatment groups. In contrast, lead exposure failed to cause any change in serum LH and FSH levels, whereas cadmium and combined treatments showed significant decrease in serum LH and FSH levels as compared with control. The accumulation of both metals increased in the hypothalamus and pituitary after treatment. These data suggest that the metal accumulation disrupts the regulatory mechanisms of the hypothalamic–pituitary axis where the effects produced by the combined treatment of metals are not additive.

Effects of nicotine on the hypothalamic-pituitary-axis (HPA) and immune function: introduction to the Sixth Nicotine Round Table Satellite, American Society of Addiction Medicine Nicotine Dependence Meeting, November 15, 1997.

This meeting was the sixth consecutive Nicotine Round Table Satellite Meeting which was held in Washington, DC, on 15 November, 1996; previous meetings are presented in Table I. The overall objective of these meetings was to bring together scientists and clinicians as a means of developing a dialogue concerning the basic mechanisms of nicotine action and the effects of nicotine on the whole organism. The specific topic of this meeting was chosen because of the potent effects of nicotine on the hypothalamic-pituitary-axis (HPA), and newer concepts indicating that the immune system and the HPA are connected via a variety of neuroendocrine and neurotransmitter elements. Whereas the HPA appears to play a unique role in adapting to internal and external stressors, the immune system appears to act as a forward scout which provides information important to the HPA. This Satellite Meeting evaluated the effects of nicotine from three points of view: (1) the effects of nicotine on HPA function; (2) the effects of the HPA on the pharmacological effects of nicotine; and (3) the effects of nicotine on immune function. This specific presentation will provide an overview of the findings of the meeting and will discuss several of the overriding issues in this area of nicotine research.