Two hours following intraperitoneal injection, estradiol-H3 is concentrated by cells in a system of limbic and hypothalamic structures. Preoptic-hypothalamic nuclei containing estrogen-concentrating cells include the medial preoptic area, medial anterior hypothalamus, ventromedial nucleus, arcuate nucleus and ventral premammillary nucleus. Limbic structures include the medial and cortical nuclei of the amygdala, lateral septum, bed nucleus of the stria terminalis, diagonal band of Broca, olfactory tubercle, ventral hippocampus, and prepiriform and entorhinal cortex. Labelled cells were also found in the lateral and ventrolateral portions of the mesencephalic central grey. Compared to these regions, most other regions of the nervous system, including the spinal cord, have very small numbers of labelled cells, which are relatively weakly labelled, and are not found in regular, specific locations. The distribution of estrogen-concentrating cells determined with the present autoradiographic method agrees with previous autoradiographic conclusions and with biochemical results from cell fractionation experiments.

The locations of estrogen-concentrating cells coincide in several brain regions with locations of estrogen-dependent neuroendocrine control mechanisms, as determined by brain implants, lesions, electrical stimulation, and electrophysiological recording. Moreover, experimental neuroanatomical studies have provided evidence for several pathways connecting regions which concentrate radioactive estradiol. Taken together, the evidence suggests a limbic-hypothalamic system of estrogen-concentrating neurons which participate in the control of mating behavior and of gonadotrophin release from the pituitary.

Atlas of estradiol-concentrating cells in the central nervous system of the female rat.

Gonadotropin-releasing hormone (GnRH) neurons and their pathways in the rat brain were localized by immunocytochemistry in 6- to 18-day-old female animals, by use of thick frozen or vibratome sections, and silver-gold intensification of the diaminobenzidine reaction product. GnRH-immunoreactive perikarya were observed in the following regions: olfactory bulb and tubercle, vertical and horizontal limbs of the diagonal band of Broca, medial septum, medial preoptic and suprachiasmatic areas, anterior and lateral hypothalamus, and different regions of the hippocampus (indusium griseum, Ammon's horn). In addition to the known GnRH-pathways (preoptico-terminal, preoptico-infundibular, periventricular), we also observed GnRH-immunopositive processes in several major tracts and areas of the brain, including the medial and cortical amygdaloid complex, stria terminalis, stria medullaris thalami, fasciculus retroflexus, medial forebrain bundle, indusium griseum, stria longitudinalis medialis and lateralis, hippocampus, periaqueductal gray of the mesencephalon, and extracerebral regions, such as the lamina cribrosa, nervus terminalis and its associated ganglia. By use of the silver-gold intensification method we present Golgi-like images of GnRH perikarya and their pathways. The possible distribution of efferents from each GnRH cell group is discussed.

Gonadotropin-releasing hormone (GnRH) neurons and pathways in the rat brain

Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats.

Experimental evidence supports the concept of the hypothalamus as the primary neural substrate for neuroendocrine regulation of hypophyseal hormone secretion. However, research over the last few decades has established the importance of the limbic system in the mediation of endocrine expression. Functioning as an integrative mechanism for interoceptive, exteroceptive and emotional information, the limbic system communicates with lower brain stem structures and the higher neopallial systems through extensive afferent and efferent connections. Therefore, in consideration of the enormous variety of autonomic and behavioral responses elicited by external factors or experimental manipulation of the various components of the limbic system, and of the fundamental role of the endocrines in the maintenance of homeostasis, it is not surprising that activation of the endocrine system should follow disturbances to limbic structures. Research over the last ten years has focused on elucidating the nature of the interactions of various limbic structures with the hypothalamus.

Effects of Lesions and Electrical Stimulation of the Amygdala on Hypothalamic-Hypophyseal-Regulation

De- and regeneration of brain serotonin neurons following 5,7-dihydroxytryptamine treatment: Effects on serum LH, FSH and prolactin levels in male rats

Ovaric and uterine hypertrophy in the rat bearing mesencephalic lesions.

In order to study the integrative action of the mesencephalon in the control of gonadotrophic secretion, bilateral electrolytic lesions were placed in two different sites: the periaqueductal gray matter (PGM) and the reticular formation proper (MRF).

Comparative study of ovarian hypertrophy and estral cycle in rats with two different mesencephalic lesions.

Sex differences of the response of the adrenal gland of the rat to mesencephalic lesions.

Lesions in the Periaqueductal Gray Matter of the Mesencephalon of the male rat result in a “castration like” pituitary and an increase of the weight of the testicles which is probably due to an increased secretion of FSH. Since estrogens have a well known inhibiting effect on gonadotrophin secretion, the effect of small doses of estradiol dipropionate (2 μg./rat/day) during one month in young-adult male rats with small bilateral electrolytic lesions in the Periaqueductal Gray Matter was studied. They were compared with castrated and normal animals which received the same dosage of estrogen. Endocrine organs were carefully weighed and studied histologically to ascertain their functional state. Quantitative studies were performed upon the adenohypophysis determining the rate of cell types and the size of “gonadotroph” basophils. In non operated animals, this dosage of estrogen provoked a diminution in the secretion of ICSH which was revealed by a marked diminution of the weight of the ventral prostate; and also provoked a diminution of FSH which was hardly enough to induce a small decrease of testicular weight, without deleterious effects on the seminiferous epithelium. In animals bearing lesions in the Periaqueductal Gray Matter a potentiation of the inhibiting effects of estrogen on gonadotrophin secretion was obtained, which resulted in a marked decrease of the weights of the testicles and the ventral prostate, with more marked regressive changes of the Leydig cells than those of the seminiferous epithelium. Since the administration of reserpine to rats bearing lesions in the Periaqueductal Gray Matter has been found to bring about an increase of the weight of the testicles, it may be inferred that the caudal pole of thelimbic system of NAUTA may regulate either activating or inhibiting influences which control gonadotrophin secretion.

N. J. Reissenweber

Papers

Ovaric and uterine hypertrophy in the rat bearing mesencephalic lesions.

Comparative study of ovarian hypertrophy and estral cycle in rats with two different mesencephalic lesions.

Sex differences of the response of the adrenal gland of the rat to mesencephalic lesions.

Effects of estrogen on the pituitary-gonadal axis of rats bearing lesions in the Periaqueductal Gray Matter.

The action of reserpine on the endocrine system of rats bearing brain stem lesions.