Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunosympathectomy produced by treatment of newborn rats with antibodies to nerve growth factor (NGF) delays ovarian development and disrupts estrous cyclicity. While these alterations have been ascribed to loss of sympathetic neurons innervating the ovary, the treatment also causes partial loss of ovarian sensory innervation. The present experiments were undertaken to determine if selective interference with ovarian noradrenergic/sympathetic action would result in alterations of ovarian development similar to those caused by NGF antibodies (NGF Ab). We have used two approaches to disrupt catecholamine action on ovarian cells: 1) inhibition of beta-adrenoreceptors by local delivery of receptor blockers to the ovaries of juvenile rats; and 2) elimination of the sympathetic innervation by long term postnatal treatment with guanethidine (GD), an adrenergic neuron blocking agent. When GD is administered chronically it produces an autoimmune-mediated destruction of peripheral sympathetic nerves, without affecting cholinergic or sensory neurons. Of the receptor blockers tested, FM-24, a nonreversible antagonist, resulted in a sustained 70% decrease in available receptors throughout the 10-day period studied. In spite of this, the timing of puberty, assessed by the age at vaginal opening and first ovulation, was not delayed, suggesting that activation of the remaining receptors by an intact innervation suffices to maintain a normal noradrenergic influence. GD treatment initiated at the end of the first week of postnatal life and maintained for three weeks slowed the juvenile-peripubertal rate of body growth, delayed the time of vaginal opening and first ovulation, and disrupted subsequent estrous cyclicity, but did not affect the animals' fertility. The ovaries of GD-treated rats exhibited a striking loss of sympathetic (norepinephrine and neuropeptide Y) nerves but a normal sensory innervation (represented by fibers containing calcitonin gene-related peptide). The concentration of beta-adrenoreceptors in granulosa cells was reduced, suggesting follicular immaturity. Direct assessment of this inference by morphometric analysis of the ovaries revealed that follicular development was retarded. The progesterone and estrogen response of juvenile ovaries to gonadotropins in vitro were also reduced. At this time, circulating LH levels were slightly decreased, but neither LHRH content in the median eminence nor the LHRH response to prostaglandin E2 in vitro were affected.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Guanethidine-mediated destruction of ovarian sympathetic nerves disrupts ovarian development and function in rats. 197 80

The density and distribution of nerve fibres immunoreactive to antisera for PGP 9.5 (general neuronal marker), calcitonin gene related peptide (CGRP) and substance P (SP) (markers for sensory neurons), as well as neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and tyrosine hydroxylase (TH) (markers for autonomic fibres), were examined in the temporomandibular joint (TMJ) of late gestation fetal sheep. This work formed part of a project investigating the influence of age and osteoarthritis on the innervation of the TMJ, and was undertaken to determine whether the innervation of the joint at 140 d gestation (17 d before birth) differed from that in the mature adult. Immunofluorescence microscopy was applied to serial sections of the capsule, disc and synovial membrane of 10 joints from 5 fetuses and image analysis was used for the quantitative assessment. The capsule, synovial membrane and the disc contained fibres immunoreactive (IR) to antisera for PGP 9.5, SP and CGRP. NPY-IR fibres were only visible in the loose connective tissue of the capsule. No VIP- or TH-IR nerve fibres were detected in the fetal TMJ. There was no statistically detectable difference between the density of nerve fibres immunoreactive to CGRP or PGP 9.5 antisera in the capsule or disc. Substance P-immunoreactivity (IR) was relatively weak in all samples examined. Scattered branches of CGRP-IR fibres were found deep in the disc proper. The lack of receptor endings, other than free nerve endings in the TMJ of the late fetal sheep, might be a reflection of the functional and anatomical immaturity of the TMJ, as reflected in the immature, gross and microscopic appearance of the disc, the inferior joint compartment and articular surface of the condyle at this stage. These results demonstrate that the capsule, synovial membrane and disc in the TMJ of fetal sheep at 140 d gestation age are innervated with sensory fibres, while autonomic fibres are located in the capsule only. The findings also support the view that the disc is innervated at an early stage of life but at a later stage the density of innervation in the central part of the disc regresses and the innervation remains only peripherally in the adult TMJ disc. Further work is required to determine (1) at what stage sympathetic fibres innervate the disc and the synovium, and (2) when the mechanoreceptive nerve endings develop.
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PMID:Distribution and coexistence of neuropeptides in nerve fibres in the temporomandibular joint of late gestation fetal sheep. 930

The discovery of leptin has generated an extraordinary interest in the field of obesity but also in the understanding of the relationship between metabolic status and the neuroendocrine system. Following the initial demonstration that leptin administration to fasting mice can 'protect' neuroendocrine secretions and prevent the changes that are associated with fasting, the concept has emerged that a normal leptin secretion is a prerequisite for normal neuroendocrine secretions. Several unfavorable metabolic situations are associated with low plasma leptin, increased secretion of hypothalmic neuropeptide Y (NPY), and hypogonadism, and a causal relationship has been evoked. Severe dietary restriction in juvenile female rats is associated with low plasma leptin and sexual immaturity. Cessation of food restriction leads to immediate increase in plasma leptin followed 4 days later by vaginal opening. If food restriction is maintained, central leptin infusion can induce sexual maturation, thus demonstrating that leptin can act as a signal for the onset of puberty. In untreated type-I diabetic rats, hypogonadism is associated with very low plasma leptin and increased hypothalmic NYP synthesis and oestrous cyclicity. Fasting rapidly inhibits growth hormone (GH) secretion in association with low plasma leptin and elevated hypothalmic NPY. Central infusion of leptin to fasting rats was able to completely prevent the collapse of GH secretion and to maintain a normal low NPY synthesis. In summary, normally elevated plasma levels appear to be a prerequisite for normal GH and gonadotropin secretion in the rat. Degradation of metabolic conditions results in a rapid reduction of circulating leptin that could represent the signal for several alterations of neuroendocrine secretions. At the level of the hypothalamus, leptin could act on NPY neurons to transduce part or all of this 'metabolic' message. The possibility that changing plasma levels for leptin also affect peripheral endocrine targets, such as pituitary, ovary, adrenal or pancreas, is likely since these endocrine organs express functional long-term leptin receptors.
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PMID:Metabolic control of sexual function and growth: role of neuropeptide Y and leptin. 972 77