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Levels of the murine sex-limited protein (Slp) were measured by an enzyme-linked immunosorbent assay in normal and hypophysectomized female CDF1 (Slpa) mice before and after a 15-day treatment with testosterone proprionate. Both groups of mice initially had undetectable levels of circulating Slp. After treatment, Slp serum levels of the nonhypophysectomized group had risen significantly above the Slp serum levels of the hypophysectomized group and the pretreatment controls. This indicates that the pituitary gland is necessary for the androgen-induced expression of Slp.

This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as are findings from developing peripheral and invertebrate nervous systems. The first part of the review is concerned with the morphological maturation of synapses as described from both qualitative and quantitative perspectives. Next, epigenetic influences on synaptogenesis are examined, and later in the article the concept of epigenesis is integrated with that of hierarchy. It is suggested that the formation of synaptic junctions may take place as an ordered progression of epigenetically modulated events wherein each level of cellular affinity becomes subordinate to the one that follows. The ultimate determination of whether a synapse is maintained, modified or dissolved would be made by the changing molecular fabric of its junctional membranes. In closing, a hypothetical model of synaptogenesis is proposed, and an hierarchial order of events is associated with a speculative synaptogenic sequence. Key elements of this hypothesis are 1) epigenetic factors that facilitate generally appropriate interactions between neurites; 2) independent expression of surface specializations that contain sufficient information for establishing threshold recognition between interacting neurites; 3) exchange of molecular information that biases the course of subsequent junctional differentiation and ultimately results in 4) the stabilization of synaptic junctions into functional connectivity patterns.

Dopamine regulates the secretion of pituitary hormones: it inhibits permanently the production of prolactin and blocks the gonadotrophins and the thyroid-stimulating hormone. It stimulates inconstantly the secretion of growth hormone and it does not control corticotropin. Dopamine agonists and antagonists are currently used in the investigation and the treatment of hyper-prolactinemia and acromegaly.

A model of the interaction between endocrine function and agonistic responding was developed that incorporates three specific hypotheses about the relationship between hormones and agonistic behavior: (1) The baseline hormonal state of the organism contributes to the determination of whether, in what way, and how intensely the animal will react when it is exposed to appropriate environmental stimuli. (2) One function of the hormonal responses to environmental stimulation and behavioral experiences is to modify the continuing and future behavior of the individual in the same or similar situations. (3) Another function of these hormonal responses is to modify the individual's stimulus qualities so that other individuals' agonistic reactions to it will be modified. The data on hormones and agonistic behavior were reviewed in the context of this model, and some directions for future research were proposed.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

The widespread and lasting effect of acupuncture suggests the mediation of humoral factor(s). Controlled clinical and experimental investigations done by Chinese researchers during the past three decades lend support to this assumption. Electrophysiological and histochemical studies denote the involvement of hypothalamus and pituitary in acupuncture. Acupuncture causes the release of some of the anterior pituitary hormones, as assessed by bio-assay methods. Observations from physiological as well as morphological approach showed that acupuncture has significant influences upon thyroid, adrenal gland and gonads. Preliminary results also indicate that pancreatic islets and parathyroid gland are affected by acupuncture. However, much remains to be investigated concerning the endocrinological basis of acupuncture.

Hormones can promote or inhibit aging depending on the experimental conditions employed. The aging effects of hormones are demonstrated by reducing hormone secretion by hypophysectomy or chronic underfeeding in young or mature rats. These result in depressing whole body metabolism, growth, body temperature and blood glucose levels, heart rate and vital capacity, gene expression, etc., but delaying aging of tissues, suppressing development of pathology and tumors, and, in underfed rats, prolonging life span. The anti-aging effects of hormones are demonstrated by elevating hormone levels in old rats whose hormones have declined as a result of dysfunctions that develop in the neuroendocrine system with age. An increase of hormones in these rats promotes gene expression, elevates protein synthesis, and enhances metabolism, growth, and function of stimulated organs and tissues.

Regulation of the rapid compensatory growth seen in the remaining adrenal gland of rats following unilateral adrenalectomy is poorly understood. The role of adrenocorticotropic hormone (ACTH) is obscure as immunoneutralization of circulating ACTH does not affect the observed compensatory growth or hyperplasia. This finding, together with the fact that mechanical manipulation of one adrenal without extirpation is followed by growth only in the contralateral gland, has led to the concept of neural regulation of compensatory adrenal growth via a loop from one adrenal through the hypothalamus and back to the contralateral gland which is independent of ACTH secretion. We recently showed that peptides from the N terminal of ACTH precursor proopiocortin (POC), not containing the gamma-melanocyte-stimulating hormone (gamma-MSH) sequence, can stimulate adrenal mitogenesis and proposed that normal long-term adrenal growth and proliferation involves post-secretional proteolytic cleavage of pro-gamma-MSH [or N-POC(1-74)] to generate the mitogenic factor N-POC(1-48/49) and a C-terminal fragment N-POC(50-74), or rat gamma 3-MSH. We have now investigated this hypothesis further in rats by selectively quenching different regions of circulating POC peptides with specific antisera and observing the effect on the increases in weight, RNA and DNA normally seen in the remaining gland following unilateral adrenalectomy. Our results, reported here, suggest that neurally mediated proteolytic cleavage of the circulating inactive mitogenic precursor pro-gamma-MSH at the adrenal gland is the major mechanism of control of compensatory growth.

The pituitary hormones responsible for the maintenance of progesterone secretion by the corpus luteum have been determined by replacement therapy in hysterectomized-hypophysectomized goats and in goats hypophysectomized on day 40 of pregnancy. Progesterone concentrations were 7.2 +/- 0.81 ng/ml plasma (mean +/- S.E. of mean) in intact goats during the luteal phase of the cycle and were 5.9 +/- 0.56 ng/ml plasma after hysterectomy. After hypophysectomy of hysterectomized goats, treatment with 25 or 150 i.u. prolactin/day failed to maintain the corpora lutea, and progesterone concentrations fell to below 1.0 ng/ml plasma. Treatment with 1.0 mg luteinizing hormone (LH)/day after hypophysectomy maintained progesterone concentrations at 2.5 +/- 0.48 ng/ml and treatment with 1.0 mg LH and 150 i.u. prolactin/day resulted in increased peripheral concentrations of 12.9 +/- 1.66 ng progesterone/ml plasma. In goats hypophysectomized on day 40 of pregnancy treatment with 1.0 mg LH/day or 1.0 mg LH and 150 i.u. prolactin/day resulted in maintenance of the pregnancy and maintenance of high peripheral concentrations of 15.0 +/- 1.77 ng progesterone/ml plasma, with no difference between the two treatments. The results show that LH is the pituitary hormone primarily responsible for the maintenance of progesterone secretion by the corpora lutea in the goat and that prolactin is synergistic with LH in stimulating this function. The difference in the pituitary luteotrophic complex between non-pregnant and pregnant animals may be explained if placental lactogen can substitute for prolactin in the luteotrophic complex of pregnant goats.

To evaluate the role of the opiate-like peptidergic pathways in modulating the pituitary hormone response to stress, we measured the GH, PRL, and cortisol responses to hypoglycemia and exercise in normal subjects with and without pretreatment with naloxone, given in the centrally active dose of 0.4 mg iv. Basal serum levels of GH, PRL, and cortisol were not changed significantly by prior naloxone administration. The maximum incremental response of GH to exercise was significantly blunted (13.1 +/- 1.6 vs. 6.0 +/- 1.4; P less than 0.001) by prior naloxone administration. Pretreatment with naloxone did not affect the responses of GH, PRL, or cortisol to hypoglycemia or the PRL response to L-dopa. On the basis of these studies we conclude that the opiate-like peptidergic pathways are not important in the regulation of basal levels of GH, PRL, and cortisol and have only a modest modulating influence on the stress-induced release of the hormones, which may be obscured in the face of severe stress.

Relations between Endocrinology and Psychiatry are developing in two main directions: Behavioural effects of hormones. After the effects of peripheral hormones, recent works are concerned with A.C.T.H. and Antidiuretic Hormone (which interfere with memory process) and with Hypothalamic Peptides (which might have psychotropic properties, independant of their endocrine regulation function). -Correlations between psychiatric syndroms and endocrine disorders. In some mentally depressed patients, disorders of the hypothalamic control of Coricotrophin, Growth Hormone and Thyreo-stimulating Hormone, have been observed. As many psychotropic drugs can influence the secretion of Prolactin, a systematic survey of this hormone in various mental illnesses, is suggested.

The hypothesis that pituitary hormones are required for increased fibrinogen synthesis after inflammation or endotoxin was tested by measuring plasma fibrinogen concentrations after inflammation or endotoxin in normal and hypophysectomized rats. Animals were divide into groups receiving no exogenous adrenal steroids, low-dose adrenal steroids, or high-dose adrenal steroids. Hypophysectomy failed to prevent fibrinogen levels from rising after intramuscular turpentine (mean 240 mg/100 ml prior to and 556 mg/100 ml 24 h after turpentine). Steroids did not suppress this rise. Endotoxin, 5 mug/100 g, caused a marked rise in fibrinogen in normal rats at 24 h (mean 296 mg/100 ml before endotoxin and 554 mg/100 ml after endotoxin). This dose of endotoxin killed hypophysectomized rats within 12 h. Hoevr, if hypophysectomized rats were protected with high-dose adrenal steroids, then 5 mug of endotoxin per 100 g caused the same fibrinogen rise as in normal rats (mean 299 mg/100 ml before endotoxin and 587 mg/100 ml after endotoxin). Aparently, pituitary hormones are not necessay for increased fibrinogen synthesis after either inflammation or endotoxin in the rat.

Although relationships between hormones of the hypothalamic-pituitary-thyroid (HPT) axis and behavior have been suspected for more than two centuries, there existed no framework within which they could be understood. It now appears that disturbances in the HPT-axis have more to do with affective state than with any other aspect of mentation, save possibly cognition. First, depression is the most frequently observed psychiatric symptom in patients suffering from hypothyroidism. Second, approximately 30% of euthyroid patients with major depression show a blunted, i.e., attenuated TSH response after TRH administration. Third, it is now well established that a small dose of thyroid hormone will accelerate the antidepressant effect of tricyclic antidepressants (TCA) in women, and convert TCA non-responders into responders in both sexes. Fourth, administration of TRH may induce an increased sense of well-being and relaxation in some patients and healthy volunteers. However, little is known about the pathophysiologic mechanism whereby evocative emotional factors express their effect on the HPT axis, or whereby thyroid gland alterations express their behavioral effects. Longitudinal, prospective studies of both patients with thyroid disease and patients with depression (through close collaboration between endocrinology and psychiatry) are most likely to separate cause and effect in most instances.

The evaluation and treatment of pineal region tumors has changed dramatically in the past decade. New imaging techniques result in earlier diagnosis. Surgical techniques now permit removal of benign tumors (about one third of cases). Pathologic diagnosis is obtained for the remainder, and postoperative therapy can be planned rationally. Germ cell tumors pose a particularly difficult problem for the pathologist because they often contain mixed germ cell elements. Biologic markers, beta HCG and AFP, aid diagnosis and can be monitored in serum and CSF to assess response to treatment. Only boys develop precocious puberty with pineal tumors. What appears to be puberty is actually pseudoprecocious puberty, due to ectopic production of HCG by their neoplasms (choriocarcinomas or germinomas with syncytiotrophoblastic giant cells). HCG can stimulate tests to produce testosterone, but FSH is necessary (together with LH or HCG) to stimulate ovaries to produce estrogen. Diabetes insipidus with pineal tumors is usually due to spread to the hypothalamus by ventricular seeding, but we report a case of aqueductal stenosis with diabetes insipidus resulting from a massively dilated third ventricle. Rarely, hydrocephalus may trigger true precocious puberty, a syndrome easily differentiated from pseudoprecocious puberty by endocrinologic tests. There are no biologic markers to diagnose pineal parenchymal tumors. Elevation of melatonin in plasma or CSF and increased tumor biosynthetic activity has been reported in isolated cases, but the range of melatonin values in normals is very wide, and melatonin levels do not correlate with specific pathologic tumor types. Both parenchymal and nonparenchymal tumors may increase melatonin nonspecifically by interfering with regulatory mechanisms of the normal pineal gland.

The metabolic response to surgery causes sodium and water retention. It does not seem logical to pour crystalloid solutions into patients in the peri-operative period, particularly when these solutions can cause deterioration in lung function. Plasma volume must be maintained to prevent a decreased blood flow to vital organs such as the kidneys. Blood or colloid solutions, not crystalloid solutions, should be used for this purpose, since the latter are distributed throughout the whole extracellular space and are less effective in maintaining plasma volume. Water given as 5% dextrose should be given in minimal quantities to maintain intracellular hydration. Patients undergoing minor to moderate surgery when they are likely to be drinking within 24 hours do not usually require any intravenous infusion. Moreover, to administer intravenous fluids to these patients may cause harm. No fluid regimens should be inflexible and the patient's size, age and fluid losses should be taken into account.