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The effects of six consecutive LH-RH injections (25 μg intravenously each) at 90 min intervals on serum gonadotrophin and serum ovarian steroid levels were investigated in cyclic women (n= 13) in the follicular, midcycle and luteal phase of the menstrual cycle.The maximum responseof LH pituitary reaction to repeated LH-RH injections was smallest in the follicular phase, higher in the luteal phase and greatest in the midcycle phase of the menstrual cycle. The maximum response of FSH reaction was small both in the follicular and luteal phase and again greatest in the midcycle phase.The pituitary response patternafter six consecutive LH-RH injections also varied throughout the cycle. On the one hand there was a constant pronounced increase in the response from the first to the second LH-RH injection for both LH and FSH, while the second of all six increments (Δ2) was the maximum increment. On the other hand, for both LH and FSH the responses Δ3to Δ6decreased progressively in the luteal phase and showed an even further pronounced decrease in the midcycle phase, indicating an exhaustion of pituitary secretion. In the follicular phase, however, the decrease in the responses Δ3to Δ6for LH was small, but significant. For FSH no significant changes between the responses Δ2to Δ6were observed.Secondary to the elevated gonadotrophin levels, serum levels of oestradiol, 17-hydroxyprogesterone and progesterone increased slightly in the follicular phase and distinctly in the luteal phase of the cycle.Possible mechanisms are discussed which might provide an explanation for the observed augmentation and subsequent diminution of pituitary reaction.

In 17 euthyroid normal volunteers and 17 hypothyroid patients, serum concentrations of TSH, T3and T4were measured after multiple stimulations with TRH. All subjects received 6 TRH-injections (200 μg iv) at intervals of 2 h. Three euthyroid normal volunteers were stimulated 12 times with TRH in the same way.The TSH response (ΔTSH) was significantly decreased (P<0.01) after the 4th injection, and after the 5th of 6th stimulation, it was significantly raised (P<0.02) compared with the 4th. In the case of the 12-fold stimulations, the ΔTSH also rose after the 9th or 10th injection compared with the response after the 8th of 9th.In 5 of the 17 normals, the increase in ΔTSH observed after the 5th or 6th TRH-injection was greater than the ΔTSH after the first stimlation.Serum T3and T4levels rose already after the first TRH-stimulation (P<0.01) and remained at these increased levels thereafter.The hypothyroid patients also showed initial decrease of ΔTSH (P<0.01). The increase of the TSH-response to TRH, however, was observed after the 4th TRH-injection (P<0.05) rather than after the 5th or 6th, followed by another decrease of ΔTSH after the 5th stimulation (P= 0.02). In 11 of the 17 hypothyroid patients, there was a second increase of ΔTSH after the 6th TRH-stimulation. This second increase was greater than the first in 10 of the 11 subjects. Serum T3and T4levels in the hypothyroid subjects remained unchanged during the entire examination period.From these results, it can be concluded that the cause for the TSH response pattern in TRH-stimulations repeated at brief intervals cannot be due to the feed-back of thyroid hormones, but rather to the activity of TSH-producing pituitary cells.

The objective of this study was to re-investigate the capacity of pituitary prolactin (Prl) and thyrotrophin (TSH) secretion throughout the normal menstrual cycle to respond to repeated thyrotrophin releasing hormone (TRH) stimulation analogous to the double luteinizing hormone-releasing hormone (LRH) stimulation test. This test has been shown to be a sensitive parameter for oestrogenic effects on the gonadotrophs. In addition, the volunteers were selected carefully on the basis of ovulatory cycles and otherwise normal endocrine function.In 9 women a combined LRH/TRH double stimulation test was performed during the early follicular, periovulatory and mid-luteal phases. TRH (200 μg) and LRH (25 μg) each were given iv twice, 2 h apart.Basal and LRH stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found to follow characteristic cyclic response patterns. The LH responses after both LRH stimulations were greatest in the periovulatory phase; Δ1and Δ2were higher in the mid-luteal phase than in the follicular phase. Maximum FSH response to LRH was found during the periovulatory phase, but the FSH response in the early follicular phase was greater than that found in the mid-luteal phase. In contrast, basal and TRH stimulated serum concentrations of TSH and Prl remained constant throughout the cycle.The gonadotrophin ratios Δ2:Δ1were generally greater than 1. They increased from 1.4 in the early follicular phase to 3.0 in the late follicular phase, concomitant with the rise in oestrogens. The Δ2: Δ1ratios for TSH and Prl were less than 1, ranging from 0.66 to 0.98 for TSH and from 0.26 to 0.99 for Prl. They did not show any cyclic changes.Thus, this study shows that after LRH/TRH double stimulation, the gonadotrophin but not the Prl and TSH responses vary with the physiological changes in oestrogens during the menstrual cycle.The supposed mechanism of oestrogen effects on pituitary hormone secretion and their possible clinical significance are discussed.