Age and time-of-day differences in the hypothalamo-pituitary-testicular, and adrenal, response to total overnight sleep deprivation.

Study Objectives: In young men, sleep restriction decreases testosterone (Te) and increases afternoon cortisol (F), leading to anabolic-catabolic imbalance, insulin resistance, and other andrological health consequences. Age-related differences in the hypothalamo-pituitary-testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk. We aimed to evaluate and compare the 24-h and time-of-day effect of sleep restriction on F, luteinizing hormone (LH), and Te in young and older men.

Dynamic Interactions Between LH and Testosterone in Healthy Community-Dwelling Men: Impact of Age and Body Composition.

Background: Aging is associated with diminished testosterone (Te) secretion, which may be attributed to Leydig cell dysfunction, decreased pituitary stimulation, and altered Te feedback.

Objective: To study all regulatory nodes-gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and Leydig cell-in the same cohort of healthy men.

Study Design: This was a placebo-controlled, blinded, prospectively randomized cross-over study in 40 men, age range 19 to 73 years, and body mass index (BMI) range 20 to 34.

Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women.

Background: Oral administration of estradiol (E2) generally increases GH secretion in postmenopausal women. Oral administration of E2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied.

Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

Context: Quantitative studies of the short-term feedback of testosterone (T) on luteinizing hormone (LH) secretion in healthy men are relatively rare. Such studies require the shutting down of endogenous T secretion and the imposition of experimentally controlled IV T addback.

Objective: To evaluate whether pulsatile and continuous T delivery confers equivalent negative feedback on LH secretion.

Estradiol Does Not Influence Lipid Measures and Inflammatory Markers in Testosterone-Clamped Healthy Men.

Context: Experimentally controlled studies of estrogenic regulation of lipid measures and inflammatory cytokines in men are rare.

Objective: To delineate the effect of estradiol (E) on lipids and inflammatory markers.

Design: This was a placebo-controlled, single-masked, prospectively randomized study comprising experimentally degarelix-downregulated healthy men [n = 74; age 65 years (range, 57 to 77)] assigned to four treatment groups: (1) IM saline and oral placebo; (2) IM testosterone and oral placebo; (3) IM testosterone and oral anastrozole (aromatase inhibitor); and (4) IM testosterone, oral anastrozole, and transdermal E for 22 (±1) days.

Differential Effects of Estradiol and Progesterone on Cardiovascular Risk Factors in Postmenopausal Women.

Context: Controlled, blinded studies of sex-hormone replacement in postmenopausal women using natural estradiol (E) and native progesterone (P) are few.

Objective: To delineate the effect of E alone or with P on lipids and inflammatory markers.

Design: A placebo-controlled, double-masked, prospectively randomized study of 40 healthy, postmenopausal volunteers assigned to four treatment groups: placebo, intramuscular E, and/or micronized oral P for 23 (±2) days.

Effects of Toremifene, a Selective Estrogen Receptor Modulator, on Spontaneous and Stimulated GH Secretion, IGF-I, and IGF-Binding Proteins in Healthy Elderly Subjects.

Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene.

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

Objective: Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses.

Methods: This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23).

Estrogen-like potentiation of ghrelin-stimulated GH secretion by fulvestrant, a putatively selective ER antagonist, in postmenopausal women.

Context: Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause.

Objective And Design: The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion.

Setting: The study was performed at the Mayo Center for Clinical and Translational Science.

Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning.

A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders. Although there is a strong genetic component to anxiety disorders such as posttraumatic stress disorder (PTSD) there remains debate about whether abnormalities in amygdala function predispose to these disorders. In the present study, groups of C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice were selected for differences in volume of the basolateral amygdala complex (BLA).

Effects of repeated maternal separation on prepulse inhibition of startle across inbred mouse strains.

A growing body of research implicates genetic factors and childhood trauma in the etiology of neuropsychiatric diseases such as schizophrenia. However, there remains little understanding of how genetic variation influences early life stress to affect later disease susceptibility. Studies in rats have shown that postnatal maternal separation (MS) results in later deficits in prepulse inhibition of the acoustic startle response (PPI), an impairment in sensorimotor gating found in schizophrenic patients.

Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice.

Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory.

Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior.

Rationale: Galanin and its receptors exert inhibitory neuromodulatory control over brain monoamines. Rat studies revealed that galanin expression is upregulated by exposure to stressors and that galanin manipulations modify neuroendocrine and behavioral responses to stress, leading to the hypothesis that galanin mediates depression-related behaviors.

Methods: In the present study, we examined the role of galanin in modulating antidepressant-related behavior in galanin overexpressing transgenic (GAL-tg) mice and galanin receptor R1 knockout (GAL-R1 KO) mice, using the tail suspension test (TST).

Mice lacking the serotonin transporter exhibit 5-HT(1A) receptor-mediated abnormalities in tests for anxiety-like behavior.

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission via clearance of extracellular serotonin. Abnormalities in 5-HTT expression or function are found in mood and anxiety disorders, and the 5-HTT is a major target for antidepressants and anxiolytics. The 5-HTT is further implicated in the pathophysiology of these disorders by evidence that genetic variation in the promoter region of the HTT (SLC6A4) is associated with individual differences in anxiety and neural responses to fear.

Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze.

The neuropeptide galanin coexists with norepinephrine and serotonin in neural systems mediating emotion. Previous findings suggested that galanin modulates anxiety-related behaviors in rodents. Three galanin receptor subtypes have been cloned; however, understanding their functions has been limited by the lack of galanin receptor subtype-selective ligands.

Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter.

Inhibition of the serotonin transporter (5-HTT) is a principal initial target of many antidepressants. However, the contribution of the 5-HTT to their therapeutic efficacy is incompletely understood. We utilized a targeted gene mutation approach to examine the role of the 5-HTT in the behavioral actions of antidepressants.

Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice.

Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US).