Search Results

ABSTRACT

The serum levels of FSH and LH were determined in 11 normal menstrual cycles by radioimmunoassay. The results of LH assay demonstrated a consistent pattern with a sharp 3 to 4 fold increase occurring on the average 13.9 days before the next menses. The changes in FSH levels during the cycle were neither as marked nor as consistent. Three distinct patterns seemed to emerge. However, the mean levels of FSH from the 11 cycles demonstrated a significant high level 12 days before, a low level 1 day before and another rise 1 day after the midcycle peak of LH.

Abstract. In hyperprolactinaemic patients with amenorrhoea, pulsatile secretion of LH is reported to be infrequent or absent. For further assessment of the effect of prolactin (Prl) on LH pulsatility, the serum gonadotrophin concentration was determined at 15 min intervals for 180 min in 12 patients with prolactinomas before treatment and in 6 patients who showed normalization of the Prl level after trans-sphenoidal surgery.

Surgical treatment caused a significant reduction (P < 0.05) of the mean (± se) serum Prl level from 519 ± 152 to 9.2 ± 1.4 ng/ml. The mean LH level (7.3 ± 1.2 mIU/ml) before treatment was significantly increased (P < 0.05) after trans-sphenoidal surgery (12.7 ± 2.4 mIU/ml). An LH spike was defined as an LH concentration that exceeded the mean LH level over the study period by 2 sd of the intra-assay variation, achieving a level of above 10 mIU/ml. LH spikes were observed in 2 of 12 patients (16.7%) before treatment, and in 5 of 6 patients (83.3%) after trans-sphenoidal surgery, the difference being significant (P < 0.05).

These results suggest that hyperprolactinaemia in prolactinoma patients may cause impaired LH pulsatile secretion and that this derangement can be reversed by reduction of the Prl level by adenomectomy.

ABSTRACT

In order to assess the effect of hyperprolactinaemia on the ovarian response to exogenous gonadotrophin, serum oestrogen levels were determined in 6 normal females. Two hundred and twenty-five IU of human menopausal gonadotrophin (hMG) was im injected daily for 3 days from the 4th day of the menstrual cycle, and the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and oestradiol-17β were determined by radioimmunoassay daily for 7 days starting from the first day of injection (control cycle). After 2 months the same schedule was applied to the previous 6 subjects and in addition sulpiride 100 mg bid was given orally during the course of the study (sulpiride cycle).

There was a significant increase in serum FSH and a decline in serum LH during hMG treatment in both groups. The mean (± se) serum levels of PRL in the sulpiride group increased gradually from 24.5 ± 3.8 ng/ml (1st day) to 56.2 ± 3.4 ng/ml (7th day). All these levels were significantly higher than those of the control group. The mean (± se) serum oestradiol increments by hMG stimulation in control and sulpiride groups showed a peak on the 5th day with respective levels of 757.2 ± 202.3 and 845.3 ± 263.3 pg/ml. No significant differences in the mean oestradiol increment were found between the two groups on any day.

These results indicate that acute hyperprolactinaemia does not appear to induce ovarian refractoriness to exogenous gonadotrophin in normal cyclic women.

ABSTRACT

The response of serum LH to exogenous oestrogen administration was studied in 5 patients with testicular feminization syndrome (TFS).

The serum LH levels were elevated in all the patients, while serum testosterone levels were within the normal male range. Serum FSH levels were elevated in 4 patients and normal in one patient. Intravenous administration of 100 μg of LH-RH provoked a further increase in both LH and FSH. Following intravenous injection of 20 mg of conjugated oestrogen (Premarin®), the LH levels were serially determined until 120 h in TFS patients, 5 normal males, and 10 normal females during the mid-follocular phase (D_7-9). Both TFS patients and normal males showed no LH release following oestrogen injection in contrast to normal females who displayed a significant increase in LH with a peak at 48 to 56 h after the injection.

These results seem to suggest that the insensitivity of the hypothalamus to androgen in TFS patients do not affect the sex differentiation of the hypothalamus. The possible role of oestradiol conversion from testosterone in the hypothalamus is discussed.

Abstract. The effect of hydrocortisone on the release of luteinizing hormone (LH) and LH-releasing hormone (LRH) in response to clomiphene citrate (clomiphene) were examined in a sequential double chamber perifusion system by perifusing the mediobasal hypothalami (MBH) and/or pituitaries excised from normal female rats in dioestrus. When the MBH and the pituitary were perifused in sequence with medium containing 5 × 10⁻⁶ m hydrocortisone, a significant release in LH (100– 150% increase, P < 0.01–P < 0.05) was observed 40 min after the administration of 3 × 10⁻⁸ mol clomiphene. Clomiphene had no effect on LH release from the pituitary when perifused in series with the MBH without basal hydrocortisone infusion. Administration of clomiphene did not cause a significant increase in LH from the pituitary perifused alone, with or without medium containing hydrocortisone. The concentration of LRH in the efflux was significantly increased 40 min after clomiphene administration when MBH was perifused with medium containing hydrocortisone, whereas clomiphene had no effect when perifused with medium only. These data indicate that hydrocortisone stimulates the effect of clomiphene on LRH release from the hypothalamus, which in turn induces LH release from the pituitary.

Abstract. A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single ip administration of 5 μg oestradiol-17β (E₂) to long-term ovariectomized rats did not induce LH surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E₂ could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear oestrogen receptors (ER) were also examined in the pituitaries of these animals. An ip injection of 200 μg clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels remained almost unchaged for 72 h. An administration of E₂ 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. However, LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E₂ was injected 48 h after the clomiphene administration. The E₂-induced LH release seems to be induced by a replacement of clomiphene by E₂ on the nuclear receptor complex. These results suggest that clomiphene may exert actions directly on the pituitary gland to augment oestrogeninduced LH release.

Abstract.

The effect of hyperprolactinaemia on the hypothalamo-pituitary axis was assessed by iv injection of 100 μg luteinizing hormone releasing hormone (LRH) in 7 women with prolactinoma before and 3 months after normalization of the Prl level by transsphenoidal surgery. A dose of 20 mg of conjugated oestrogen (Premarin®) was also injected iv into patients with prolactinoma before and 4 months after surgery, and the serum LH levels were determined serially for 120 h after the injection. Surgical treatment caused significant reduction of the mean (± se) serum prolactin (Prl) level from 123.3 ± 7.8 to 19.4 ± 5.6 ng/ml. But the differences in the basal levels of LH (11.3 ± 2.2 to 8.6 ± 1.5 mIU/ml), FSH (8.3 ± 2.4 to 10.6 ± 3.7 mIU/ml) and oestradiol (26.6 ± 8.6 to 37.5 ± 5.5 pg/ml) before and 4 months after surgery were not significant. An exaggerated LH response to LRH in untreated prolactinoma patients was also observed after surgical treatment. After surgical treatment, patients showed LH release with a peak between 48 and 72 h after the injection of Premarin, whereas before treatment they did not show any LH discharge. The mean percent increase in LH between 48 and 72 h was also significantly higher after operation than before operation. These results suggest that the hyperprolactinaemia in prolactinoma patients may cause an impaired positive feedback effect of oestrogen on LH release and that this derangement can be reversed by reduction of the Prl level by adenomectomy.

Abstract.

In order to clarify the mechanism of hyperprolactinaemic anovulation, the medial basal hypothalamic (MBH) catecholamine (CA) turnover and LRH concentration, and the serum levels and pituitary contents of gonadotrophins and prolactin (Prl) in hyperprolactinaemic female rats were examined. Hyperprolactinaemia (HPrl) was produced by oral administration of sulpiride for 10 consecutive days; each measurement made on the sulpiride-treated rats was compared with that of control dioestrus rats. Prl, LH, FSH and LRH were determined by radioimmunoassay; CA turnover, as assessed by the accumulation of CA following monoamine oxidase inhibition, was assayed by high performance liquid chromatography with electrochemical detection. Sulpiride treatment induced (1) an increase in the serum Prl and a decrease in the serum LH, (2) an increase in the pituitary FSH and LH contents, (3) an increase in the MBH LRH concentration, and (4) an increase in the MBH dopamine (DA) turnover. These results suggest that HPrl may induce anovulation by impaired LH secretion which was caused by the suppression of LRH release due to an increase in DA turnover in the MBH.

Abstract. The effect of prostaglandin D₂ on the release of luteinizing hormone was studied in a superfusion system by superfusing human pituitary gland. Perfusion with 30 μg of prostaglandin D₂ induced a significant increase of luteinizing hormone secretion. This is the first evidence of a direct effect of prostaglandin D₂ on the secretion of luteinizing hormone from the human pituitary gland. This finding suggests the possible role of prostaglandin D₂ in human reproductive function

Abstract.

The effects of insulin-like growth factor-I on gonadotropin release were studied using primary culture of rat anterior pituitary cells incubated with IGF-I (20-5000 μg/l) and a hypothalamus-pituitary perifusion system, in which either the mediobasal hypothalamus-pituitary unit or the pituitary were perifused with IGF-I (20-2000 μg/l). In primary cultures of rat anterior pituitary cells, IGF-I (2000 μg/l) caused a significant increase in the release of both LH (46% increase) and FSH (27% increase). It also caused a significant decrease in the cellular content of LH (9%) and FSH (19%). Its effects in stimulating gonadotropin release were suppressed by administration of anti IGF-I receptor antibody (1 mg/l). In the perifusion system, IGF-I (2000 μg/l) did not affect the LH release from the hypothalamus-pituitary or pituitary alone. However, it caused a significant increase in the GnRH (10⁻⁹ mol/l) stimulated LH release from perifused pituitary. These data suggest that IGF-I enhances pituitary gonadotropin release via the IGF-I receptor, but its effect on the hypothalamus was not confirmed.