Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release

Despite intense investigation, the demonstration of morphological plasticity in the external zone of the median eminence concerning the gonadotropin-releasing hormone system has never been reported. In this study, we investigate whether dynamic transformations of the gonadotropin-releasing hormone nerve terminals and/or tanycytes in the external zone of the median eminence of the hypothalamus occurred during the rat estrous cycle, by following individual gonadotropin-releasing hormone-immunoreactive nerve terminals on serial ultrathin sections observed by electron microscopy. Female rats were killed at 16.00 diestrus II (n = 3), i.e. when estrogen levels are basal and gonadotropin-releasing hormone release is low, and at 16.00 proestrus (n = 4), i.e. when estrogen levels peak and the preovulatory gonadotropin-releasing hormone surge occurs. Our results show that, in the median eminence obtained from proestrus rats, 12+/-2% of the gonadotropin-releasing hormone nerve terminals were observed to make physical contact with the parenchymatous basal lamina, i.e. the pericapillary space. In the median eminence obtained from diestrus II rats, no contacts were observed. On proestrus, numerous physical contacts between gonadotropin-releasing hormone nerve terminals and the basal lamina occurred by evagination of the basal lamina and/or by emerging processes from gonadotropin-releasing hormone nerve terminals. The quantification of the evagination of the basal lamina revealed that the basal lamina was at least twofold more tortuous in appearance during proestrus. These results demonstrate for the first time the existence of dynamic plastic changes in the external zone of the median eminence, allowing gonadotropin-releasing hormone nerve terminals to contact the pericapillary space on the day of proestrus, thus facilitating the release of the neurohormone into the pituitary portal blood.     

Cranial base kyphosis and the surface morphology of the anterior cranial fossa.

We investigated the relationship between the surface morphology of the anterior cranial fossa and cranial base kyphosis (sphenoid angle) in 52 cephalometric craniograms. Among them there were 25 female (mean age 54 +/- 15; range 31-82) and 27 male (mean age 43 +/- 18, range 19-85) skulls. The sphenoid angle and the altitudes of the highest elevation of the endofrontal eminence (cranial base over the orbital roof in the anterior cranial fossa) and the middle point of the sphenoid planum, measured according to the Frankfort horizontal, were analysed using classical cephalometric and morphometric analysis. Statistical analysis was performed by Pearson's product-moment correlation and simple linear regression. The sphenoid angle ranged from 97 degrees to 137 degrees (mean 118 +/- 9 degrees). The altitude ratio of the highest elevation of the endofrontal eminence and the middle point of the sphenoid planum ranged from 1.5 to 1.8 (mean 1.6 +/- 0.1). A significant correlation was found between this ratio and the sphenoid angle (r = -0.65; p < 0.001; coefficient of determination = 0.43). The elevation of the endofrontal eminence relative to the sphenoid planum was higher in skulls with increased cranial base kyphosis, whereas reduced sphenoid angle was associated with an increase in the elevations of the endofrontal eminence. Although the sphenoid angle has a significant effect on the morphology of the anterior cranial fossa, only 43% of the variance in altitude of the endofrontal eminence is likely to be explained by its relationship with the sphenoid angle.     

Axovascular relationships in developing median eminence of perinatal rats with special reference to luteinizing hormone-releasing hormone projections

Topographical relationships of neurosecretory axons with the capillaries of the primary portal plexus were studied in the median eminence of rats from the 14th fetal till the 9th postnatal day by means of electron microscopy combined with morphometric analysis. Special attention was given to the light and electron microscopic immunocytochemical examination of luteinizing hormone-releasing hormone projections to the median eminence. Neurosecretory axons possessing secretory granules and clear microvesicles were first observed in the median eminence at the 14th fetal day. However, all of them were situated at a distance from the primary portal plexus. By the 20th fetal day, neurosecretory axons reached the external basal lamina of the primary portal plexus giving rise to so-called axovascular contacts. Some axons even penetrated into the perivascular space, apparently facilitating the neurohormone delivery into the hypophysial portal circulation. From that time on, both the number of the axons abutting on the external basal lamina and the entire area of axovascular contacts increased gradually. As to luteinizing hormone-releasing hormone axons, they grew into the median eminence from the 18th fetal day concentrating in older fetuses and neonates either over the primary portal plexus, or around the infundibular recess of the 3rd ventricle. After birth, the concentration and distribution of luteinizing hormone-releasing hormone axons within the median eminence became similar to those of adults. Luteinizing hormone-releasing hormone axons were found to arise from the neurons of septopreoptic area including the diagonal band of Broca. These data suggest the onset of neurohormone release in the median eminence from the 14th fetal day followed by the establishment of the hypothalamic control over the pituitary functions during the perinatal period in rats.     

Anatomical relationships of serotoninergic and noradrenalinergic projections with the GnRH system in septum and hypothalamus

Summary Immunahistochemical double staining for gonadotropin releasing hormone (GnRH) and serotonin or dopamine--hydroxylase reveals close appositions of fibers which contain serotonin or norepinephrine to GnRH producing neurons in the septo-preoptic region. In the organum vasculosum of the lamina terminalis and in the median eminence extensive anatomical overlap exists in the distribution of GnRH and serotoninergic fibers but little of GnRH and noradrenalinergic fibers. It is proposed that serotonin plays a major role in the regulation of GnRH secretion via contacts in all of the regions studied and that the influence of norepinephrine on GnRH-secretion in the median eminence is exerted mainly via involvement of dopaminergic tuberoinfundibular neurons.Supported by the Deutsche Forschungs-Gemeinschaft Je 105/2, US PHS grant NS09914, and HD03110 to the Biological Sciences Research Center, Chapel Hill     

Resistance vessels supplying the median eminence of the rabbit, rat, and cat

The ultrastructure of arterioles supplying the median eminence of eight rats, eight rabbits, and two cats was studied after vascular perfusion with phosphate buffered aldehyde fixatives. There were terminal arterioles with a lumen diameter of 50-70 micron within the pars tuberalis. Smaller arterioles (precapillary sphincters and metarterioles) with a lumen diameter of 15-20 micron were present on the surface of the median eminence. Arterioles were not observed to penetrate the neuropil but were seen to supply the external capillary plexus of the median eminence. Direct innervation of arterioles supplying the median eminence was not present and hence regulation of median eminence blood flow by peripheral sympathetic mechanisms appears unlikely. Resistance vessels were found to be closely related to axon terminals on the surface of the median eminence and to fenestrated capillaries of the external plexus. In addition, the endothelial cells of arterioles were characterized by the presence of pits and vesicles which may play a role in transendothelial transport. These findings suggest two mechanisms by which blood flow into the median eminence can be regulated: (a) by central catecholaminergic systems terminating in the median eminence and (b) by catecholamine secretions from the adrenal medulla.     

利用CT薄层扫描技术研究弓状隆起与上半规管的位置关系

目的　探讨Fisch法在颅中窝手术入路中如何识别弓状隆起，分析弓状隆起与上半规管的相对位置关系。 方法　选取18~57岁无颞骨岩部占位性病变的受试者60例，其中男女各30例，左右双侧共120个样本，颞骨CT薄层扫描并建立三维坐标系，测量弓状隆起、上半规管的三维坐标值并分析两者的位置关系。 结果　弓状隆起的形态不定，约有15.00%的样本弓状隆起不明显，导致无法定位；弓状隆起与上半规管并非严格对应，约有83.75%的样本弓状隆起位于上半规管的后外侧。 结论　Fisch法进行内耳道手术时，部分样本弓状隆起的识别存在困难；大部分上半规管并不在弓状隆起下方，弓状隆起多位于上半规管的后外侧。     

利用CT薄层扫描技术研究弓状隆起与上半规管的位置关系

目的　探讨Fisch法在颅中窝手术入路中如何识别弓状隆起,分析弓状隆起与上半规管的相对位置关系。 方法　选取18~57岁无颞骨岩部占位性病变的受试者60例,其中男女各30例,左右双侧共120个样本,颞骨CT薄层扫描并建立三维坐标系,测量弓状隆起、上半规管的三维坐标值并分析两者的位置关系。 结果　弓状隆起的形态不定,约有15.00%的样本弓状隆起不明显,导致无法定位;弓状隆起与上半规管并非严格对应,约有83.75%的样本弓状隆起位于上半规管的后外侧。 结论　Fisch法进行内耳道手术时,部分样本弓状隆起的识别存在困难;大部分上半规管并不在弓状隆起下方,弓状隆起多位于上半规管的后外侧。     

Anatomical relationships of dopaminergic and GABAergic systems with the GnRH-systems in the septo-hypothalamic area

Summary Immunohistochemical double staining for gonadotropin releasing hormone (GnRH) and tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD) reveals in the septo-preopticdiagonal band complex of the rat brain close spatial associations between GnRH-immunoreactive perikarya and TH and GAD immunoreactive fibers. In the organum vasculosum laminae terminalis, no close spatial relationships could be observed between TH-or GAD-positive fibers and the GnRH-containing system. In contrast, in the median eminence substantial overlap exists in the distribution of GnRH with TH and GAD containing nerve fibers. This overlap is most intense for TH throughout the lateral palisade zone, while for GAD it is more restricted to the outermost portion of the external palisade zone. The results suggest that dopamine and GABA influence GnRH secretion via axosomatic contacts in the septo-preoptic-diagonal band complex, as well as via axo-axonic interactions in the median eminence, while no such interactions seem to exist in the organum vasculosum laminae terminalis. Since dopaminergic cell bodies in the ventral hypothalamus are closely apposed by GnRH and GAD containing fibers, the existence of feedback circuits among GnRH, dopamine and GABA systems is proposed.     

腓肠神经营养血管皮瓣的真性吻合连接及修复前足创面的疗效

目的　报道并分析腓肠神经营养血管皮瓣修复前足创面的临床疗效。 方法　选取5例肿瘤患者高位截肢的下肢标本,冲洗和灌注后,剥离体被组织摄X线片,观察腓肠神经营养动脉链内、腓动脉穿支间及这些穿支与动脉链间的真性吻合连接。临床行腓肠神经营养血管皮瓣修复前足创面52例。 结果　标本观察发现,腓肠神经营养动脉链内从踝间线至腘窝横纹、腓动脉远端2~3个穿支间及这些穿支与动脉链间均通过真性吻合连接。临床研究中皮瓣成活42例;部分坏死10例,予以1例Ⅱ期缝合、8例植皮、1例局部皮瓣转位后残留创面愈合。 结论　腓肠神经营养动脉链内、腓动脉远端2~3个穿支间及这些穿支与动脉链间的真性吻合连接,是腓肠神经营养血管皮瓣存活长度较长的血管解剖学基础,该皮瓣是修复前足创面的一种较好方法。     

Morphological changes in the hypothalamic arcuate nucleus and median eminence in the golden hamster during the neonatal period

The purpose of the present investigation was to study the ultrastructure of the arcuate nucleus (ARC) and median eminence of hamsters on days 1–15 of the neonatal period. From days 1–6, the neurons of the ARC had large nuclei and a small amount of cytoplasm which contained polysomes, mitochondria, RER, lysosomes and Golgi complexes. From days 7–15 there was an increase in the amount of cytoplasm as well as more extensive Golgi complexes and RER. Astrocytes were the predominant glial component in both the ARC and median eminence. Astrocytic processes were in juxtaposition to unmyelinated axons, dendrites, and synapses. Axodendritic and axosomatic synapses containing clear vesicles were observed in the neuropil on day 1. There was an increase in the number of dense-core vesicles in the axonal endings beginning on day 4. Concomitantly, there were increasing numbers of clear and dense-core vesicles (64–70 nm) in terminals of the external layer of the median eminence, whereas larger dense-core vesicles (105–140 nm) were distinguishable by day 10 immediately dorsal to the external layer. The capillaries of the median eminence were composed of nonfenestrated endothelium from days 1–9. Fenestrae began to appear about day 10. Ependymal cells lining the third ventricle had pinocytotic vesicles, microvilli, and bleb-like protrusions on their apical surfaces. Ependymal processes were adjacent to nerve processes in the neuropil of the ARC and in the external layer of the median eminence, where they contacted the perivascular space. Two types of supraependymal cells were seen in animals throughout the neonatal period. One resembled a neuron which sent processes along the ependymal surface and often between cells. The second type was similar to a macrophage. The results of this study demonstrate the maturation of the neural elements in the ARC/median eminence area of the neonatal hamster.     

颞骨内面神经垂直段的显微解剖及其临床意义

目的：研究颞骨内面神经垂直段及其毗邻结构的显微解剖,为临床应用提供解剖学资料。方法：通过模拟临床经乳突入路的方法,分层解剖20个成人湿性头颅标本（40侧颞骨）,显露并观测颞骨内面神经垂直段及其毗邻结构。结果：面神经垂直段的长度为（17.39±1.78）mm、直径为（2.13±0.13）mm,面神经垂直段与水平段的夹角（向前）为（115.5±6.89）°,面神经垂直段近端至外半规管隆突距离为（2.86±0.31）mm,鼓索神经自面神经发出点至茎乳孔距离为（5.99±0.74）mm,面神经垂直段与鼓索神经的夹角（向上）为（38.6±1.99）°,锥隆起尖到面神经垂直段垂直距离为（2.05±0.65）mm,后半规管至面神经垂直段最短距离为（2.89±0.36）mm。有5%（2/40侧）的面神经垂直段的近端位于外半规管隆突外侧。结论：外半规管、鼓索神经、茎乳孔、锥隆起、后半规管是手术中确定面神经垂直段的重要标志。熟悉颞骨内面神经垂直段与其周围结构的毗邻关系,有利于面神经垂直段相关手术的顺利进行。     

Scanning microscopy of pituitary vascular casts

Vascular casts of the pituitary-median eminence complex from seventeen adult female rabbits were examined with the scanning electron microscope. The results of this study confirm the presence of a single capillary bed common to the entire neurohypophysis. Arterial supply to the rabbit pituitary is only to the neurohypophysis. A direct supply to adenohypophysis was not found. Within the median eminence there are an external and internal capillary plexus. The internal capillary plexus is directed toward the infundibular recess of the third ventricle. It does not receive a direct arterial supply but derives its blood supply from the external plexus before draining to the adenohypophysis. Vessels of the posterior median eminence are confluent with vessels of the infundibular stem. On the basis of these studies, it is proposed that the entire neurohypophysis, not simply the median eminence, serves as the final common pathway to the glandular pituitary. It is also proposed that in the median eminence, vessels are organized to deliver blood containing hypothalamic releasing and inhibiting hormones as well as posterior lobe neural hormones (antidiuretic hormone and oxytocin) to the ventricular surface for subsequent transport to cerebrospinal fluid and distribution to the brain.     

Programmed cell death and the morphogenesis of the hindbrain roof plate in the chick embryo

The spatial and temporal distribution of apoptosis in the dorsal midline of the developing chick hindbrain was examined in relation to the development of the neuroepithelium and neural crest using scanning and transmission electron microscopy, immunocytochemistry and in situ hybridization. The pattern of TUNEL labeling and Slug expression in the dorsal midline at stages 10 and 11 differed from that at stages 12-15. At stages 10 and 11, TUNEL labeling and Slug expression were observed in the dorsal part of location II of rhombomere 1/2 (i.e., between the surface ectoderm and the neuroepithelium), but from stage 12 onward, they were observed in both the dorsal and ventral parts of location II. The implication is that whereas apoptosis may be restricted to a subpopulation of the early migrating neural crest at stages 10 and 11, it presumably occurs in subpopulations of both neural crest and neuroepithelial cells from stage 12 onward. Furthermore, as judged by the pattern of TUNEL labeling and Slug expression in r3 and r5, apoptosis in these two rhombomeres likely occurs in subpopulations of both neural crest and neuroepithelial cells. The eminence present in location I of r1/r2 between stages 10 and 12 consisted of both neural crest and neuroepithelial cells. These cells gradually underwent apoptosis until stage 12, when the eminence disappeared in most embryos. The formation of the inner (neuroepithelial) aspect of the hindbrain roof plate involved both cell migration from adjacent neuroepithelium and an alteration in the shapes of the cells, such that cells with flattened surfaces eventually lined the roof plate. During these processes, some of the neuroepithelial cells underwent apoptosis (i.e., in location IV). The results of this study thus demonstrate that subpopulations of both neuroepithelial and neural crest cells may be involved in programmed cell death in the hindbrain. Additionally, apoptosis in the hindbrain contributes significantly to morphogenetic thinning during roof plate formation.     

Origin of the nerve endings in the surface zone of the median eminence of the rat hypothalamus

Summary In order to study the origin of the nerve endings in the surface zone (zona palisadica) of the median eminence and the proximal part of the pituitary stalk, experiments were designed to determine the extent of the smallest region of the brain, isolation of which does not result in terminal degeneration in this zone. Various hypothalamic areas were partially or totally separated from the brain by means of a stereotaxically manipulated bayonet-shape knife and the zona palisadica was examined for secondary degeneration of axon terminals under the electron microscope. If the medial basal hypothalamus, including the suprachiasmatic area was disconnected from the rest of the brain, degenerated nerve endings do not occur in the palisade zone. Axon degeneration is observed if any part of the medio-basal area was separated from the median eminence or became necrotic. — These findings indicate that the nerve terminals in the zona palisadica arise exclusively from neurons in the medial basal hypothalamus, and that fibers of other origin do not terminate in this zone. The present observations support the assumption that the hypothalamic releasing (and inhibiting) factors are produced by, and the neural control of the anterior pituitary is exercised over a short final neuronal link, localized in the medial basal hypothalamus.     

Post-natal development of the median eminence of the guinea pig

The ultrastructure of the median eminence of neonatal (newborn, 1-, 3-, 5-, and 10-day old) and adult guinea pigs was studied to determine the dynamic changes occurring in this structure during early life. At birth the portal vasculature consists of the Mantelplexus and a few, non-fenestrated capillary loops. The number of ansae and the degree of fenestration increase rapidly after birth. The abundance of cytoplasmic and ciliary projections into the ventricular recess and the large numbers of organelles indicate that the ependymal cells are more active in the neonatal period than in the adult male. Moreover, the ependymal endfeet cover most of the surface area of the primary portal plexus during this time. The neuronal layers of the median eminence are difficult to distinguish at birth due to the lack of myelinated fibers in the zona interna. Significant myelination appears on day 3 but is not complete until day 10. There is a progressive increase in the numbers of Herring bodies and large neurosecretory granules (1,500-1,700 Å) during this same time period. In the zona externa, few nerve terminals abut on the perivascular space until day 3. Increases in numbers of granules per axon profile were noted for each day after birth. Despite the relatively long gestation period of the guinea pig (68-72 days), the morphologic appearance of the median eminence at birth suggests that the neurovascular link controlling anterior pituitary function is not yet complete.     

血管性痴呆小鼠第三脑室室管膜扫描电镜特征观察

目的:观察血管性痴呆(VD)小鼠第三脑室正中隆起室管膜表面扫描电镜特征变化并探讨其意义.方法:采用双侧颈总动脉线结、反复缺血-再灌注法,制作小鼠VD动物模型,并设假手术组作为对照.应用扫描电镜对两组小鼠上述区域进行观察.结果:(1)假手术组:室管膜上皮细胞表面可见较多的纤毛和大量的微绒毛.分泌颗粒丰富,呈圆球形.室管膜上神经元样细胞较多,胞体饱满,呈梭形或锥体形,突起较多.(2)VD模型组:纤毛和微绒毛均明显减少,且室管膜细胞表面凹凸不平.室管膜细胞分泌颗粒明显减少,且形态各异,有皱缩现象.室管膜上神经元样细胞数量减少,胞体不饱满,树突减少.结论:VD小鼠正中隆起室管膜细胞和室管膜上神经元样细胞存在着超微结构的损伤;本研究发现的上述改变是VD发生的重要病理学改变之一.     

人工耳蜗植入术的应用解剖学研究

目的探讨后鼓室入路人工耳蜗植入术的有关解剖,为人工耳蜗植入手术提供解剖学基础。方法取成人颞骨标本60侧(左、右各30侧),在放大6倍的手术显微镜下进行观察和测量,结果进行统计学处理。结果圆窗龛(窝)的形态大体分为2种类型:近圆形(52%)和近半圆形(48%)。圆窗龛下壁有一窦腔者占86.7%。岬下脚出现率为11.7%,岬小桥出现率为33.3%。颈静脉窝高位,窝顶达圆窗龛上缘者占11.7%,均未影响圆窗龛的形态。外耳道上棘至锥隆起、鼓索隆起、圆窗龛前唇(缘)、面神经管锥曲的距离分别是(18.02±1.21)mm、(15.22±1.32)mm、(20.09±1.20)mm、(14.96±2.03)mm。鼓索隆起至面神经管锥曲、锥隆起的距离分别是(3.33±0.42)mm、(3.79±0.56)mm。锥隆起向后至面神经管的距离平均为(3.58±0.47)mm。结论后鼓室进路即是通过面神经隐窝的进路,面神经隐窝大小各异,鼓索隆起至面神经管锥曲和至锥隆起的距离,可作为面神经隐窝的宽度。人工耳蜗植入术经面神经隐窝入路较理想,距圆窗龛较近,有利于电极插入。该入路靠近面神经管,手术操作时应注意保护面神经。圆窗龛前唇遮盖圆窗膜,手术时必须磨去前唇暴露圆窗膜。     

An electrophysiological and morphological investigation of the projections of growth hormone-releasing peptide-6-responsive neurons in the rat arcuate nucleus to the median eminence and to the paraventricular nucleus

Growth hormone-releasing peptide-6 injection induces c-fos messenger RNA expression in many arcuate nucleus neurons, and sub-populations of neurons in this region project to the hypothalamic paraventricular nucleus. We examined electrophysiologically whether arcuate nucleus neurons that project to the paraventricular nucleus also project to the median eminence, and whether these neurons are activated by systemic injection of growth hormone-releasing peptide-6. Of 116 arcuate nucleus neurons tested, 43 were antidromically-identified as projecting to the paraventricular nucleus and a further 30 as projecting to the median eminence; these populations displayed distinct electrophysiological characteristics, and contrasting patterns of orthodromic response to stimulation of the median eminence and paraventricular nucleus, indicating that these two populations are functionally distinct with limited communication between them. Only one cell was antidromically-identified as projecting to both these regions. Three of 10 arcuate nucleus neurons that projected to the paraventricular nucleus were activated by injection of growth hormone-releasing peptide-6. In parallel experiments, we examined whether Fos protein expression is induced in arcuate nucleus neurons that project to the paraventricular nucleus, as identified by retrograde-labelling with FluoroGold. Immunocytochemical studies revealed that 20% of arcuate nucleus neurons that were retrogradely-labelled from the paraventricular nucleus were Fos-positive following growth hormone-releasing peptide-6 injection, although cells that were both Fos-positive and retrogradely-labelled accounted for less than 5% of the total number of Fos-positive arcuate nucleus neurons. These results confirm that there is a direct projection from the arcuate nucleus to the paraventricular nucleus and indicate that growth hormone-releasing peptide-6 activates some of these neurons.     

A second look at the barriers of the medial basal hypothalamus

The cell bodies of hypothalamic secretory neurons are localized in areas protected by the blood-brain barrier (BBB), whereas their axon terminals are localized in the median eminence, which lacks a BBB. This implies a complex barrier system, allowing neurons of the central nervous system to secrete into the blood stream without making the BBB leaky. In the present study, three experimental protocols were applied to clarify certain relevant aspects of the barriers operating in the medial basal hypothalamus of the rat. We established that the milieu of the arcuate nucleus is exposed to both the ventricular and the subarachnoidal cerebrospinal fluid (CSF).The median eminence milieu, the perivascular space of the portal vessels, and the subarachnoid space appear to be in open communication; also, beta2-tanycytes establish an efficient barrier between the median eminence milieu and the ventricular CSF. Similarly, beta1-tanycytes establish a lateral barrier, separating the intercellular space of the median eminence from that of the arcuate nucleus. We also found that the glucose transporter I (GLUT I), a BBB marker, is localized throughout the whole plasma membrane of beta1-tanycytes, but is missing from beta2-tanycytes. Expression of GLUT I by tanycytes progressively develops during the first postnatal weeks; while the degree of damage of the arcuate nucleus by administration of monosodium glutamate, at different postnatal intervals, parallels that of the GLUT I immunoreactivity of beta1-tanycytes. An explanation is offered for the selective destruction of the arcuate neurons by the parenteral administration of monosodium glutamate to infant rats.     

Immunohistochemical localization of gonadotropin-releasing hormone (GnRH) in the fetal and early postnatal mouse brain

The objectives were to (a) determine the age in development when GnRH is first detectable in the brain and (b) observe the distribution of GnRH throughout the fetal and early postnatal period. GnRH was localized immunohistochemically in fetal (15, 16, 17 and 19 days of gestation) and early postnatal (1- and 7-day-old) mice with the peroxidase-antiperoxidase (PAP) method of Sternberger. In the organum vasculosum of the lamina terminalis (OVLT) and in the median eminence of the fetus, GnRH was first detected at 17 days of gestation. In the OVLT, GnRH was found ventral to the preoptic recess of the third ventricle near the ventral surface of the brain. In addition, GnRH was located adjacent to the superficial portal capillaries near the surface of the median eminence. At 19 days of gestation, the distribution of GnRH was similar to that observed at 17 days and there was a marked increase in amount. In the newborn mouse, GnRH was undetectable in the OVLT and its content in the median eminence was decreased as compared to that observed in the fetus. By the seventh postnatal day, a considerable accumulation of GnRH had occurred in the OVLT and median eminence. In the OVLT, it was associated with capillaries ventral to the preoptic recess, and its distribution in the median eminence was similar to that in the adult mouse. In both the OVLT and median eminence of the fetal and early postnatal mouse GnRH appeared to be stored in axons and axon endings, but was not detectable in nerve cell bodies or ependymal cells. These observations suggest that the potential for neuroendocrine control of gonadotropin secretion exists in the fetal mouse as early as 17 days of gestation.