Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple endocrine determinations were carried out on 101 patients with anorexia nervosa. Ninety-five percent of the patients studied were female, and in 94% of patients the anorexia nervosa began before 30 years of age. Evidence of gonadal dysfunction was the predominant manifestation, both clinically and by laboratory studies. Amenorrhea occurred before or concurrent with onset of weight loss in 65% of the women. The average weight loss was 28% of the weight before illness began. In an additional 11%, the disease began before menarche. The mean age of menarche in patients with secondary amenorrhea was 13 years. Urinary excretion of pituitary gonadotropin was undetectable in 44 of 65 patients and was below 19 rat units per 24 hours in the remaining patients. Serum luteinizing hormone level was below 8 microgram/dl in 15 of 27 patients studied and serum follicle-stimulating hormone was below 10 microgram/dl in 7 of 27 patients studied. Mean serum or urinary estrogens, or both, were low in more than 50% of the patients. Elevation of serum corticosteroids or loss or reversal of diurnal variation, or both, was noted in 50% of patients. Fasting serum growth hormone levels were elevated in 45% of the patients. Mean total and free serum thyroxine, thyroid-stimulating hormone, and triiodothyronine levels were low. These hormonal alterations in the hypothalamic-pituitary axis in patients with anorexia nervosa probably represent adaptive and protective mechanisms for chronic starvation and weight loss.
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PMID:Hypothalamic-endocrine dysfunction in anorexia nervosa. 92 47

Reproductive capacity of female hamsters, as estimated by the ovulatory response, is particularly susceptible to interference by food deprivation. Previous studies showed that hamsters generally fail to ovulate if deprived of food for one or two estrous cycles. The present work demonstrates that starvation which is specific to the 2 days immediately after ovulation will block the next expected ovulation in approximately 80% of the animals. Such phasic starvation also resulted in significantly smaller ovarian follicle sizes. When placed with vigorous males, anovulatory animals failed to show lordosis behavior unless exogenous estradiol benzoate (EB) was supplied. With EB provided, all animals showed short-latency lordosis. These bioassay data suggested that poorly developed follicles were secreting insufficient estradiol for the facilitation of lordosis. Exogenous luteinizing hormone (LH) given 6 h before lights off on cycle day 4 failed to elicit ovulation, further suggesting that the follicles were not mature. Radioimmunoassay of LH and follicle-stimulating hormone (FSH) levels during the ovulatory gonadotropin surge showed that LH was vastly reduced, whereas FSH was in the low-to-normal range. Estradiol levels, assayed immediately before the gonadotropin surge, were low compared with controls, whereas progesterone levels were higher than normal. The results suggest that ovulatory failure in response to phasic food deprivation is a joint function of absence of an ovulatory LH surge and a set of immature follicles.
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PMID:Environment and hamster reproduction: responses to phase-specific starvation during estrous cycle. 376 65

The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator presides over the pulsatile and feedback-regulated activities of the pituitary-gonadal axis. Awakening of synchronous activity of the GnRH neuronal ensemble in the earliest stages of puberty heralds the onset of full activation of the reproductive axis in girls and boys. Progression from prepuberty to adulthood in boys is directed by marked (30-fold) amplitude enhancement of pulsatile luteinizing hormone (LH) secretion, as assessed by an ultrasensitive immunofluorometric assay and deconvolution analysis. There is a much less apparent rise in LH secretory burst frequency (approximately 1.3-fold increase). Consequently, human puberty is an amplitude-driven neuroendocrine maturational process. However, less is known about pulsatile follicle-stimulating hormone (FSH) release in puberty. Multiple pathophysiologies that result in hypogonadotropic hypogonadism can converge on a final common mechanism of attenuated hypothalamic GnRH pulse generator output and hence reduced LH (and FSH) secretion. Disturbances may take the form of reduced GnRH pulse frequency and/or attenuated GnRH secretory burst mass. When the pathophysiology of hypogonadism originates exclusively in a failed GnRH pulse generator, then either treatment of the primary disease process where possible (e.g., by refeeding in starvation, improved metabolic control in diabetes mellitus, dopamine agonist treatment in hyperprolactinemia, etc) and/or treatment with pulsatile GnRH (e.g., in Kallmann's syndrome, isolated hypothalamic lesions, etc.) can provide relevant therapeutic options in children and adults.
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PMID:Neuroendocrine mechanisms mediating awakening of the human gonadotropic axis in puberty. 879 95

We compared the estradiol/progesterone-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release between normally fed and leptin-supplemented starved ovariectomized female rats and studied also the effect of hyper-leptinaemia on the steroid-induced hormonal release in normally fed ovariectomized rats. Three days' starvation completely abolished steroid-induced LH and FSH release. Significant recovery of the hormonal release was shown in the leptin-supplemented starved group. The magnitudes of LH and FSH release in the normally fed animals with a higher dose of leptin were statistically the same as those in the normally fed group without leptin. These observations indicate that physiological concentrations of circulating leptin exert a stimulatory effect on steroid-induced LH and FSH release.
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PMID:Effect of leptin on LH and FSH release in ovariectomized rats. 1533 May 66

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells.
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PMID:Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model. 2296 62

Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons.
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PMID:AgRP to Kiss1 neuron signaling links nutritional state and fertility. 3041 85

Severe dietary restriction, catabolic states and even short-term caloric deprivation impair fertility in mammals including human, which is often reversible by restoration of the energy supplementation. The dysregulated crosstalk among multiple organs is possibly involved in this process. However, ideal experimental animal models are needed to illuminate functional crosstalk among distal organs during the starvation pathogenesis. We have recently discovered that conditional hepatic HRD1 gene deletion results in elevated energy expenditure and consequently leads to growth retardation and female fertility. Herein, we discovered that both growth retardation and female infertility of liver-specific HRD1 knockout mice could be fully rescued by additional energy supplementation upon HFD feeding. Hepatic HRD1 deletion appears to impair by the pituitary gland functions in secreting critical hormones in growth and female fertility including growth hormone (GH), follicle-stimulating hormone (FSH) and luteinizinghormone (LH) because a dramatic reduction in the sera levels of all three hormones were detected in liver HRD1 KO mice, which consequently shortened their tibia lengths and impaired the ovary functions in females. HFD feeding for six weeks largely restored all three hormones in liver HRD1 KO mice back to levels comparable with those in WT mice. In addition, the growth hormone induced activation of JAK-STAT5 pathway was inhibited by HRD1 deletion, and additional energy supplementation upon HFD feeding restored STAT5 transcriptional activation. Our studies establish a unique mouse model to study liver crosstalk with distal organs in regulating energy balance in growth and female fertility.
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PMID:Energy supplementation rescues growth restriction and female infertility of mice with hepatic HRD1 ablation. 3250 96