Acute ethanol treatment lowers hypophyseal portal plasma luteinizing hormone-releasing hormone (LH-RH) and systemic plasma LH levels in orchidectomized rats

Acute ethanol (EtOH) treatment resulted in a significant decline in hypophyseal portal plasma levels of luteinizing hormone-releasing hormone (LH-RH) in orchidectomized rats. This was accompanied by a similar decrement in circulating luteinizing hormone (LH) without, however, modifying plasma follicle-stimulating hormone (FSH) levels at time when peak blood alcohol concentrations occurred. Thus, acute alcohol intoxication lowers circulating LH levels primarily by impairing hypothalamic neuronal secretion of LH-RH into the portal blood.     

Blockade of progesterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine.

The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.     

The pars tuberalis of the rhesus monkey secretes luteinizing hormone

The presence of luteinizing hormone within the pars tuberalis of the adenohypophysis and its secretion into pituitary stalk vessels were investigated in adult rhesus monkeys. Portal blood was collected in 9 monkeys, after section of the pituitary stalk. In 22 out of 26 samples, portal to peripheral LH ratios, as measured by radioimmunoassay, ranged from 2 to 48. Portal LH levels were highest in 3 animals studied at the time of the midcycle surge. No differences between portal and peripheral growth hormone (GH) and prolactin levels were observed. Immunocytochemical studies in 4 normal and 3 ovariectomized female monkeys indicated that LH, but not GH, prolactin or thyroid stimulating hormone were present within the pars tuberalis. Cells containing these hormones were identified within the pars distalis. These results indicate that the pars tuberalis forms and secretes LH via the hypophyseal portal circulation.     

Effects of Bovine Follicular Fluid on Pulsatile Secretion of Gonadotrophin-Releasing Hormone and Gonadotrophins in Ovariectomized Ewes

Ovariectomized ewes were injected with charcoal-extracted bovine follicular fluid (n = 5) or with hypophysectomized ewe serum (n = 5) after which hypophyseal portal blood samples were taken to monitor the release of gonadotrophin-releasing hormone (GnRH). Peripheral blood samples were also taken to monitor plasma luteinizing hormone and follicle-stimulating hormone (FSH) concentrations. Bovine follicular fluid treatment caused a 50% decrease in plasma FSH concentrations whereas hypophysectomized ewe serum did not significantly alter plasma FSH levels. The frequency and amplitude of luteinizing hormone and GnRH pulses was similar in both experimental groups. It is concluded that inhibin activity in bovine follicular fluid selectively suppresses the release of FSH by direct action on the pituitary gland, with no effect on GnRH secretion.     

Blockade of progresterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine

The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with leteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 μg/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.     

Chronic hyperprolactinemia causes progressive changes in hypothalamic dopaminergic and noradrenergic neurons

Studies were undertaken to evaluate the effects of chronic hyperprolactinemia (HYP) on catecholamine concentrations and turnover rates in brain regions of the female rat. HYP was induced by inoculation of tissue derived from the prolactin secreting MtTW15 tumor. When serum prolactin (PRL) levels were moderately elevated, medial basal hypothalamus (MBH) dopamine (DA) turnover was enhanced and DA concentrations were moderately reduced. Later, as serum PRL levels increased to greater than 10 micrograms/ml, DA concentrations were further reduced and DA turnover was concomitantly reduced to below pre-tumor levels. In the preoptic area-anterior hypothalamus (POA-AH), DA concentrations were reduced as PRL levels increased and this was associated with a reduction in DA turnover. Between 5 and 8 weeks of tumor growth, DA turnover remained low, but DA concentrations increased. In the neurointermediate lobe of the pituitary (NIL) the tumor reduced DA turnover at 5 weeks only. Norepinephrine (NE) turnover, but not concentration, was reduced in both the POA-AH and MBH. Surgical removal of the tumor at 5 weeks of growth reduced serum PRL levels to near normal, but MBH DA concentrations and turnover remained depressed while POA-AH and NIL DA levels and turnover increased. Despite removal of the tumor, NE turnover remained depressed in both the MBH and POA-AH. These studies indicate that severe chronic HYP causes progressive alterations in hypothalamic catecholamine neurons which are not reversed by normalization of serum PRL levels. These results suggest that chronic HYP can cause long-lasting effects on some DA and NE neuronal systems.     

CLINICAL EVALUATION OF THE LUTEINIZING HORMONE-RELEASING HORMONE (LH-RH) TEST IN CASES WITH ANATOMICALLY VERIFIED DISORDERS OF THE HYPOTHALAMO-PITUITARY REGION

The effect of slow intravenous infusion of luteinizing hormone-releasing hormone (LH-RH) on serum LH was studied in 58 patients with anatomically verified hypothalamo-pituitary disorders as well as in control groups. Normal responses to the LH-RH test were found in 15 out of 15 cases with intrasellar pituitary tumours and in five out of six cases after transsphenoidal surgery for an intrasellar pituitary tumour. Twenty-one out of 25 patients where a pituitary tumour with both supra- and intrasellar extension had been removed had pathological responses to the test. All eight patients with hypothalamic disorders, mainly tumours not directly influencing the pituitary, gave normal responses to the LH-RH tests. Out of four patients with hypothalamopituitary malformations a pathological response to the LH-RH infusion was found in three cases and a normal response in one case. The increase of serum LH after LH-RH infusion was pronounced and rather constant in males and post-menopausal women. It was more difficult to evaluate a “normal” test response in women of fertile ages because of the great variations during the different menstrual phases. It is concluded that the LH-RH test may be of importance in the investigation of patients with suspected tumours of the pituitary as well as for differential diagnosis between hypothalamic and pituitary disorders of gonadotropin secretion.     

Biochemical transmethylation of lipids and neuropeptidergic stimulation of pituitary hormone secretion

S-adenosyl-l-methionine-dependent methylation of membrane phosphatidylethanolamine to phosphatidylcholine has been shown to exist in a number of tissues including pituitary gland and to play important roles in receptor-mediated functions. The possible role of this phospholipid methylation reaction in pituitary hormone secretion has been studied. To this end, the ability of thyrotropin-releasing hormone (TRH) to release thyrotropin (TSH) and prolactin and the ability of luteinizing hormone-releasing hormone (LH-RH) to release luteinizing hormone (LH) were evaluated after inhibition of pituitary phospholipid methylation. Both TRH and LH-RH stimulated the release of their corresponding pituitary hormone in a dose-dependent manner and this stimulatory effect was inhibited in the presence of phospholipid methylation inhibitors. Non-specific stimulation of TSH release by 55 mM KCl or 0.1 mM veratridine, however, was not affected by the methylation inhibitors. The data suggest that phospholipid methylation may participate in receptor-mediated release of pituitary hormones.     

Effects of Carbamazepine on Pituitary Responsiveness to Luteinizing Hormone-Releasing Hormone, Thyrotropin-Releasing Hormone, and Metoclopramide in Epileptic Patients

Pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) was studied in 40 epileptic patients (24 men and 16 women) receiving carbamazepine (CBZ) treatment and in 29 (20 men and 9 women) untreated epileptic patients. Mean basal concentration of serum LH was significantly lower in the CBZ-treated female patients than in untreated female patients. The response of LH to LH-RH was also blunted in CBZ-treated female patients. No differences were found in basal or stimulated LH levels between the two groups of male patients. Nevertheless, the mean basal concentration of serum prolactin (PRL) was lower and the response of PRL to TRH was higher in male patients treated with CBZ. No differences were found in serum levels of follicle-stimulating hormone (FSH) or in responses of FSH to LH-RH between the CBZ-treated and untreated patients. These results indicate that CBZ has effects on pituitary responsiveness.     

Serum Steroid Hormones and Pituitary Function in Female Epileptic Patients During Carbamazepine Therapy

Ten regularly menstruating women with epilepsy were studied in a 12-month prospective follow-up study to evaluate the short-term effects of carbamazepine (CBZ) on serum sex hormone balance and pituitary function. Thirteen female epilepsy patients receiving long-term CBZ monotherapy (mean medication duration 5.3 years) were also studied. Controls were 17 regularly menstruating healthy volunteers. Untreated patients had higher free testosterone (FT) and luteinizing hormone (LH) serum concentrations than control subjects, whereas the other parameters did not differ between these two groups. However, serum sex hormone binding globulin (SHBG) levels increased and dehydroepiandrosterone sulfate (DHEAS) levels decreased during CBZ treatment. Although calculated free androgen index (FAI) decreased during CBZ therapy, the directly measured FT levels remained unaltered. These changes were found after 2 months and continued after 12 months of CBZ treatment. Moreover, patients with long-term CBZ also had high SHBG levels, low serum DHEAS levels, and low FAI values. Basal LH serum levels decreased during the first year of CBZ treatment and luteinizing hormone-releasing hormone (LH-RH)-stimulated LH concentrations were lower after 2 months of CBZ treatment. Although the serum basal follicle-stimulating hormone (FSH) and prolactin (PRL) levels were unaffected during the first year of CBZ therapy, the LH-RH-stimulated FSH concentrations and metoclopramide (MC)-stimulated PRL concentrations were lower after 12 months of CBZ treatment than before CBZ. Both basal and stimulated gonadotropin and PRL serum levels of long-term CBZ patients were unaffected. No changes were found in estradiol (E2), testosterone (T), or cortisol (C) serum concentrations during short or long-term CBZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)