P. Marrama

Age-Related Changes in Plasma Dehydroepiandrosterone Sulphate, Cortisol, Testosterone and Free Testosterone Circadian Rhythms in Adult Men

The circadian rhythms of serum luteinizing hormone, follicle-stimulating hormone, testosterone (T), free testosterone (fT), sex hormone-binding globulin (SHBG), oestradiol, cortisol and dehydroepiandrosterone sulphate (DHA-s) have been investigated in 5 normal male adults and 6 elderly men. Circadian rhythms were detected statistically significant (p less than 0.05) by population mean cosinor analysis, for T, fT, cortisol and DHA-s in the young group. In the elderly population, serum cortisol showed a clear circadian rhythm, although with some phase modification, whereas DHA-s secretion lost its circadian rhythmicity. This demonstrates that ageing differently affects the two major adrenal functions, glucocorticoid and androgenic; further, the data suggest that an independent adrenal androgen-regulating system could be selectively impaired in the older subjects. In the elderly group the loss of T circadian rhythm was confirmed, but a statistically significant circadian rhythm of fT was recorded. It was characterized by a marked phase advance and not related with the SHBG modifications found in elderly men. This finding leads us to reconsider the role of fT, which appears more sensitive than total T, in studying circadian rhythm of gonadal androgen secretion.

Acute estradiol and progesterone administration reduced cardiovascular and catecholamine responses to mental stress in menopausal women.

Steroid hormones are involved in the regulation of sympathoadrenal activity. Since the effect of sex steroids on the cardiovascular system and catecholamine secretion could also be exerted through an acute, nongenomic mechanism, we have studied the response to mental stress (color word test, CWT) in a group of 15 menopausal women during estrogen (100 µg of estradiol by patch), progesterone (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the curve of SBP was higher during placebo (2,855 ± 131 mm Hg·min) than during estradiol (2,585 ± 139 mm Hg·min) and progesterone (2,553 ± 179 mm Hg·min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental stress was higher during placebo than during estradiol administration (F = 4.3, p < 0.01). The area under the curve of epinephrine was 10,342 ± 1,348 pmol/min·l during placebo and 7,280 ± 818 pmol/min·l during estradiol (p < 0.03). The plasma glycerol levels at the end of CWT were higher during placebo (0.26 ± 0.04 nmol/l) than during estradiol (0.19 ± 0.03 mmol/l) and progesterone (0.17 ± 0.04 mmol/l) administration (p < 0.05 for both). No significant differences were found in the responses of diastolic blood pressure, heart rate, norepinephrine and cortisol to mental stress during placebo and estradiol or progesterone administration. This study demonstrates that acute steroid administration is able to modify the cardiovascular and catecholamine response to mental stress in menopausal women.

The endocrine effects of visual erotic stimuli in normal men.

Endocrine responses to erotic stimulation in the laboratory were assessed in eight normal subjects. Each subject was tested on two occasions. On one occasion only neutral stimuli were involved. After 15 min baseline, 30 min of films were shown. For the erotic condition on the other occasion, two 10-min erotic films were interspersed with 10 min of neutral film. Fifteen-minute blood samples were taken from the start of each test and continued for 5 hr after the films. Plasma was assayed for testosterone, LH, prolactin, cortisol, ACTH and beta-endorphin. Urine was collected for 4 hr before and 4 hr after the films; this was assayed for adrenaline, noradrenaline and dopamine. Sexual arousal occurred in response to the erotic films in all subjects, as shown by erectile and subjective responses. There were no significant changes in hormone or catecholamine levels following either the erotic or the neutral stimuli, except for a rise in cortisol during the neutral but not the erotic film. These results indicate that in the laboratory, substantial sexual response can occur without accompanying endocrine or biochemical changes.

Further Studies on the Effects of Pentoxifylline on Sperm Count and Sperm Motility in Patients with Idiopathic Oligo-Asthenozoospermia

Summary:  To further investigate the effectiveness of pentoxifylline (Trental) treatment in male infertility, we studied 22 young men (mean age 28.4 years) with “idiopathic” oligo‐asthenozoospermia treated for 6 months with the drug (1200 mg daily orally). Sperm concentration and sperm motility were determined before therapy, as well as after 3 and 6 months of pentoxifylline administration. Moreover, fructose concentrations in seminal fluid and sperm ATP levels were assayed before and at the end of the treatment in five semen samples. Pentoxifylline therapy significantly increased both sperm concentration and sperm motility. Sperm concentration showed a 1.5‐fold increase (p < 0.01) at the 3rd month of therapy, and a 2.0‐fold increase (p < 0.001) at the 6th month, whereas sperm motility increased by 1.8‐fold (p < 0.001) and by 2.8‐fold (p < 0.001) respectively. At the end of the treatment, fructose concentrations in seminal fluid were significantly higher (p < 0.001) than pretreatment values; in contrast, sperm ATP levels showed a significant (p < 0.05) fall. These results suggest that pentoxifylline, probably acting on the cAMP metabolism, may be an useful drug in the treatment of idiopathic oligo‐asthenozoospermia.

Circannual Rhythm of Plasma Thyrotropin in Middle-Aged and Old Euthyroid Subjects

The circannual rhythm of plasma thyrotropin (TSH) was evaluated in 8,310 euthyroid, serially independent, young, middle-aged and old men and women. A statistically significant circannual rhythm of plasma TSH was validated, by the mean group-cosinor method, in the middle-aged and old men and women (p less than 0.05), with acrophase in December, whereas the young subjects did not show any rhythm. No significant correlation was found between TSH plasma levels and free thyroxine (fT4) or ambient temperature in any group. Moreover, plasma fT4 did not show seasonal variations.

Iodinated-NPY binding sites: Autoradiographic study in the rat brain

Several authors have described the presence of iodinated neuropeptide-Y binding sites on membranes of the mammalian CNS. In the present study we show a mapping of iodinated-NPY binding sites in the rat brain using receptor autoradiography. The sections were incubated with 125I-Bolton-Hunter coupled NPY (0.5-03 nM), in the absence or presence of 1 microM cold NPY. Some autoradiograms are studied by means of an image analyzer (VDC 501 Tesak) equipped with the host computer PDP 11 Digital, in order to enhance the contrast of the labeling. A very high density of NPY receptors is present in the limbic regions (hippocampus, amygdaloid complex, septal nuclei), in the cortex, and in some thalamic nuclei, while in some hypothalamic regions (paraventricular nucleus and median eminence) we detected a lower amount of NPY receptors. At the mesencephalic level, the substantia nigra presents a very high density of NPY receptors.

Daily Modifications of 3h-Naloxone Binding Sites in the Rat Brain: A Quantitative Autoradiographic Study

The endogenous opioid peptides, the opiate receptors and several related behaviours, like opioid-mediated analgesia, show daily variations in different animal species including rats. The attempt to correlate the daily rhythm of opiate receptors in the central nervous system (CNS) to opiate related rhythmic phenomena requires an experimental approach with a high anatomical resolution, as the opioid distribution is very heterogeneous. In this paper we present the study of daily variations of 3H-naloxone binding sites in the different regions of the adult male rat brain, performed by means of quantitative autoradiography. Five rats are sacrificed at each investigated time of the day (0200, 0600, 1000, 1400, 1800 and 2200). The ligant is 3H-naloxone (4 nM), the quantification is performed by means of densitometric procedures (image analyzer Tesak VDC 501, computer Digital PDP 11, 3H-microscale). The statistical analysis is performed according to the single Cosinor method and the one-way analysis of variance followed by the multiple range test of Duncan. We analysed 33 different regions of the rat CNS, and the daily variations of opiate receptors are regionally selective. A circadian rhythm is found in the anterior cingulate cortex, hippocampal cortex, periventricular, medial, ventral, reticular and posterior nuclei of the thalamus, rhomboid, gelatinosus and rheuniens nuclei, lateral hypothalamus, locus coeruleus, grey substance of the pons, reticular formation of medulla oblongata, inferior olivary complex, medial part of the nucleus of the solitary tract and nucleus of the spinal tract of the trigeminal nerve. An ultradian rhythm is found in the medial and lateral preoptic areas, in the medial hypothalamus, in the medial and in the lateral nuclei of habenula. No significant variations during 24 hr according to the Cosinor analysis are found in the dorsal and lateral cerebral cortex, striatum, globus pallidus, bed nucleus of the stria terminalis, septal nuclei, lateral nucleus of the thalamus, cochlear nuclei, nucleus of the solitary tract, lateral and caudal parts, dorsal motor nucleus of the vagal nerve, XII and IX nerve nuclei. The amplitude of the daily variations observed ranges from 10 to 40%. Our results demonstrate the high anatomical selectivity of the daily modifications of 3H-naloxone binding sites in the rat CNS. They also indicate that quantitative autoradiography is a suitable and sensitive technique for these studies.

Morphometrical and Microdensitometrical Studies on Monoaminergic and Peptidergic Neurons in the Aging Brain

In a recent study we have characterized aging processes in transmitter-identified neurons demonstrated by immunocyto- chemistry or by radioreceptor autoradiography using computer assisted morphometry and microdensitomotry (Agnati et al. 1984). The results indicated the existence of heterogeneities in the degenerative patterns taking place in transmitter-identified nerve cells and receptors in relation to aging. It was i. a. discovered that the meso-striatal and meso-accumbens dopamine (DA) neurons underwent degeneration in the aging brain both pre- and postsynaptically, while the DA nerve terminal networks within the tuberculum olfactorium were resistant to the aging processes. Furthermore a marked and widespread disappearance of the μ- and Δ-type of opiate receptors were found in the aged brain, while the benzodiazepine binding was enhanced in several brain areas of the aging brain compared with the 3 month old rat brain. Thus, it is possible that in aging also supersensitivity development can take place in certain types of receptors such as the benzodiazepine receptors, which possibly represent co-transmitter binding sites in GABA synapses (see Guidotti et al. 1983). Instead, the GABA receptor binding sites are reduced in number in the aged brain, suggesting that some compensatory changes in aging may take place within the co-transmitter binding sites.

Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin-releasing hormone

objective The aim was to investigate whether a pulsatile discharge of LH from the pituitary Is necessary to achieve the circadian secretion of testosterone.

α2‐Adrenergic activity is normal in patients with thyroid disease

OBJECTIVE Several studies indicate an inverse relationship between the sympathetic nervous system activity and thyroid function. Altered adrenoceptor sensitivity, particularly α and β, have been described in hypothyroid and hyperthyroid patients. No information in patients with thyroid disease is available on the main mechanism regulating sympathetic nervous system outflow, i.e. the α2‐adrenoceptor pathway. In our study we evaluated α2‐adrenergic activity in patients with thyroid disease by the assessment of cardiovascular and catecholamine response to clonidine, a central a2 adrenergic agonist.