alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects.

Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists, or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.

[Lack of effect of therapy with LHRH analogs, alone or associated with flutamide, on prolactin levels in advanced prostatic carcinoma]. / Mancanza di effetti della terapia con analogo di LHRH, solo o associato a flutamide, sui livelli di PRL nel carcinoma prostatico in stadio avanzato.

Fourteen patients with advanced prostatic carcinoma have been considered. Some were treated with goserelin depot and some with goserelin depot plus flutamide; basal and stimulated PRL were studied in the two groups before and after two months treatment in order to verify a possible interference with prolactin secretion which seems to have a trophic and stimulating effect on neoplastic tissue growth. Basal PRL levels and levels after TRH infusion haven't shown significant variations between the two groups of patients. Even if relative to a short time, our results exclude PRL increase, which might be suspected with these drugs, and at last confirm the effectiveness of this treatment (LHRH analogs plus flutamide) in prostatic carcinoma.

Effect of caerulein on pituitary response to TRH in humans.

The effect of caerulein (100 ng/kg/h X 1 h) on basal as well as on thyrotropin-releasing hormone (TRH)-stimulated prolactin and thyroid-stimulating hormone (TSH) secretion was studied in healthy male volunteers. The peptide did not change the basal levels of prolactin and TSH. However, during the infusion of caerulein, prolactin response to TRH was significantly increased whereas the TSH response was decreased. These data, showing an action of caerulein (a frog peptide which mimics the biological actions of cholecystokinin) on prolactin and TSH release, suggest that cholecystokinin may be involved in the physiological control of human pituitary secretion.

Gonadotropin secretion in hyperthyroidism and hypothyroidism.

Gonadotropin patterns were evaluated in a group of 70 patients of both sexes with Graves' disease or primary hypothyroidism. Significant variations were found only in hyperthyroidism where increased basal and stimulated values of both gonadotropins, but particularly LH, occurred. Qualitative and quantitative recovery was seen when euthyroid states were achieved after treatment of hyper- and hypothyroid patients. Interactions with gonadotropin behavior were found in both sexes and in women of different ages. Direct interference on the hypothalamo-pituitary system rather than through the modulation of peripheral estrogen metabolism is suggested as the possible pathogenetic mechanism.

Impaired TSH response to TRH after intravenous ranitidine in man.

Ranitidine, given by i.v. infusion, decreased TSH response to TRH in 7 subjects. This effect, completely different from that obtained with cimetidine, suggests that the action of ranitidine is likely to be independent of H2-receptor blockade and rather may be related to the cholinergic-like effect of this drug.

[Study of GH in patients suffering from sexual impotence and abnormal glucose tolerance test (author's transl)]. / Comportamento del GH in un gruppo di pazienti con intolleranza glucidica ed impotenza erettiva.

The correlation between dopamine-serotonin systems and sexual behaviour and the influence of these two amines on GH secretion is well known. We evaluated GH responses (maximum increase (delta) after OGTT and mean increase (delta M) after insulin test) in a group of 32 males suffering from erective impotence with impotence with abnormal reaction to a glucose tolerance test. Results were compared with those obtained in a group of 13 normal controls. No significant difference in basal values and dynamic responses between the two groups was present. Our data suggest that GH doesn't decrease the tolerance to glucose in these patients. The abnormal values observed during a glucose tolerance test may be due to some agent involved in the interactions between limbic system, ventral lateral and ventral medial hypothalamic nuclei and dopamine-serotonin systems. No influence by this system on GH secretion is evident.

Gonadotropin-releasing hormone test for hypogonadic men.

Gonadotropin patterns before and after stimulation with gonadotropin-releasing hormone (GnRH) have been studied in 69 hypogonadic men of various types: patients with expansive hypothalamus--pituitary disorders before and after surgery, patients with hypogonadotropic hypogonadism, and patients with oligozoospermia or azoospermia who have primary partial or total testicular deficiency. Three characteristic gonadotropin patterns were found: (a) low basal values of LH and FSH with either absent or decreased and delayed responses; (b) normal basal values and pituitary responses above the normal range; or (c) high basal values and pituitary responses above the normal range. These gonadotropin patterns were correlated with disorders of the hypothalamus--pituitary--testis axis. The advantages and disadvantages of the GnRH test for the clinical evaluation of male hypogonadism are discussed.

[Evaluation of the pituitary reserve of gonadotropins and seminal function of the testis in subjects operated for cryptorchism]. / Valutazione della riserva ipofisaria di gonadotropine e della funzionalità seminale del testicolo nei soggetti operati di criptorchidismo.

76 patients (prepuberal, puberal and adults) who had undergone surgery for monolateral (35) or bilateral (41) cryptorchidism in childhood were studied. Testicular volume (76 cases), seminiferal function (18 cases) and pituitary gonadotropin reserve (51 cases) were evaluated. We obtained the following results: 1) the prepuberal patients had a normal testicular volume, while 70% of the puberal and adult patients had a mean testicular volume below normal levels. 2) 55.6% of the adults who underwent spermiogram had a pathological seminiferal function. 3) The number of patients whith exagerated gonadotropin response to GnRH-test increases with increasing puberal stage and reaches its highest significance after complete puberal development. These data confirm that: 1) the long permanence of one or both testis out of their natural position has a negative influence on their trophism; 2) the long-term prognosis of the tubular function of the testis after orchidopessis is poor in a high percentage of cases. 3) the endocrine anomalies which follow the early morphologic and functional changes of the cryptorchid testis are more easily detected during puberty as a reduced hypothalamic feedback of the gonadotropin secretion.

Thyrotropin and prolactin in patients with hypothalamus-pituitary diseases.

Seventy patients with hypothalamus-pituitary diseases were studied. 13 of them were studied before surgical treatment and then 15-20 days and 6 months later. A comparison was made with 59 controls. In all these subjects PRL and TSH were studied under basal conditions and after TRH stimulation. As for TSH the highest percentage of abnormal responses was found in the group of patients with chromophobe adenoma and parasellar dysplasias. This area of the pituitary appears relatively undamaged in acromegalic patients. In clinically hypothyroid patients, normal or high TSH responses to TRH were often found. As for PRL, a hyperprolactinaemia was mostly found in the group of patients with chromophobe adenoma, parasellar dysplasias and craniopharyngioma, although there was a different pattern in the TSH responses. No correlation was found between the basal PRL levels and the TSH responses to TRH. There was no significant difference in the TSH responses of the patients with PRL secreting and non-secreting chromophobe adenomas. The hypothesis of two autonomous systems is supported by the finding of differences in the functional recovery of the two pituitary areas studied at different times after surgical treatment.

LH and FSH (basal values and pituitary responses to GnRH) in hyperthyroidism.

Gonadotropin behaviour (basal plasma values and pituitary responses to GnRH) in hyperthyroid patients was studied. LH values (both basal and pituitary responses) higher than the controls were documented. Thyroid hormones seem to modulate pituitary response to GnRH for LH only in hyperthyroid patients of both sexes. In order to explain the mechanism of the action of thyroid hormones, rather than the possibility of peripheral effect on binding capacity of the proteins for circulating steroids, a central interaction at medial eminence level is suggested.

The LH/FSH ratio under basal conditions and after stimulation with GnRH in subjects with primary hypogonadism.

The authors have studied LH and FSH behaviour under basal conditions and after stimulation with GnRH in groups of subjects associated by the common denominator of more or less marked compromission of gonadal activity (subjects of both sexes in old age, affected by Sertoli cells only, Klinefelter's and Turner's syndromes ans subjects with congenital anorchia or with rudimentary testes) and have compared such behaviour with that shown by control groups. Special importance was given to the behaviour of LH/FSH ratio, which is significantly reduced in almost all the situations studied. To conclude, from the results obtained, the authors have evidence new elements to better single out the mechanism of homeostatic regulation of gonadotropic incretory system, with special consideration for what happens to FSH, and also useful indications to emphasize the semeiological use of LH/FSH ratio relevant to basal values and chiefly to incretory areas.

Possible interaction of PGF2 alpha with hypothalamus-pituitary-thyroid axis in man.

The possible interactions of PGF2 alpha on the hypothalamus-pituitary-thyroid axis are the object of this study. Firstly a significant direct effect of PGF2 alpha infusion (mg2,5/270 min) on TSH,PRL,LH,FSH and GH pituitary secretion was excluded. Thereafter the possible PGF2 alpha on PRL and TSH pituitary response to TRH was considered: in only two cases PGF2 alpha was able to increase the TSH response. Finally the Authors studied T3 response to endogenous TSH rise induced by TRH: if they consider the mean peak responses of T3 the increase is significant only when PGF2 alpha infusion is performed.

Pituitary TSH response to TRH: interrelationships with gonadal activity.

A TSH radioimmunoassay is described, which was used to investigate the behaviour of the TSH pituitary response (as measured by the secretory area) to TRH in groups of subjects of both sexes and different phases of gonadal activity. It is concluded that the TSH pituitary response is in no way affected by physiological variations in the plasma gonadal hormones. This independent behaviour of the TSH response, uninfluenced by gonadal activity, was apparently confirmed by the results in some pathological conditions (ovarian agenesis and primary male hypogonadism of various types) characterized by very low plasma levels of gonadal hormones.

[Mechanisms in the homeostatic regulation of the gonadotropin-secreting system. Circadian rhythm of gonadotropin LH]. / Sui meccanismi di regolazione omeostatica del sistema gonadotropo-secernente. Considerazioni sul ritmo circadiano della gonadotropina LH

PIP: After describing and discussing the mechanisms that control the secretion of gonadotropins and the action of their releasing factors, the study describes a series of tests in which luteinizing hormone (LH) levels were measured in both male and female healthy subjects at intervals of 4 hours and of 15 minutes, to detect possible rhythmic variations. Tests were also conducted to study the response of LH to its specific releasing factor (LRF), by measuring LH levels at different times after iv injection of LRF. The test results ruled out and daily rhythm, but revealed periodic "pulsations" in the release of LH with peaks at intervals of approximately the same duration both by day and by night. The effect of LRF appeared to be slightly higher in the morning, while in the afternoon and night it produced 2 peaks at intervals of approximately 60 minutes, possibly as a result of its double function of mobilizing LH and stimulating the synthesis of new LH.^ieng