The Two Pools of Pituitary Gonadotropin: Regulation During the Menstrual Cycle1

Abstract

Information on the relative activity and on the functional relationships between the acutely releasable (1st) and reserve (2nd) pools of pituitary LH during the course of the normal menstrual cycle was obtained via a 4 h LRF infusion (0.2 mug/min X 4 h). This was immediately followed by 3 pulses of LRF (10 mug at 2 h intervals) to assess further the size of the acutely releasable pool after activation of the reserve pool by the infusion. Our observations indicate that two functional pools of LH are present in all phases of the menstrual cycle and that comparative pool size or activity is influenced profoundly by ovarian steroid feedback as well as by the pattern of input of hypothalamic LRF. From the early to the late follicular phase, in synchrony with the rising levels of E2, the size of the 2nd pool is preferentially augmented. A small increase in the 1st pool activity is not apparent until the late follicular phase when a 5-fold increase in the size of the 2nd pool is also attained. During the mid-luteal phase and in association with relatively high progesterone (P) and E2, th large 2nd pool is maintained as in the late follicular phase but the 1st pool is strikingly smaller. Activation of the 2nd pool of LH by the LRF infusion (priming) increases the acutely releasable LH (1st pool) in all three phases of the cycle, as evidenced by an enhanced response to the 1st but not subsequent pulses of LRF at the end of the infusion as compared with non-infused controls. This priming effect is likely a reflection of activation or "shifting" of LH from the larger 2nd pool to the smaller 1st pool. It is found that this priming effect is greatest during the mid-luteal phase as compared to other phases of the cycle. During the days of mid-cycle LH surge, a dramatic reversal of the relative activity of the two pools in observed and this is manifested by an enormous increase in the activity of the 1st relative to the 2nd pool. In contrast to other phases of the cycle, the release of LH from the 2nd pool is not sustained and this premature decline in LH release despite continuous LRF infusion appears to be due to pituitary depletion of LH as evidenced by the failure of the pituitary response to pulses of LRF immediately following the infusion...

Regulation of the hypothalamic-pituitary-ovarian axis in women

“…The enlarged first pool may not be apparent without additional LH-RH treatment as imposed in our experimental conditions, and in normal circumstances, therefore, the increase in the first pool may represent a potential only. In subjects with little or no pre-existing ovarian feedback (hypogonadal women) (Yen, Tsai, Van den Berg & Rebar, 1972) or in normal women during the early follicular phase, we have demonstrated that oestrogen appears (a) to promote or to accelerate the LH-RH-dependent increase in the second gonadotrophin pool, probably through sequential processes of LH synthesis and storage, but (b) to impede LH-RH-mediated LH release Wang et al, 1976b;Yen & Lein, 1976;Hoff, Lasley, Wang & Yen, 1977).…”

“…This phenomenon is probably not due to an inhibitory effect of combined oestradiol and progesterone on LH-RH-mediated gonadotrophin release, but occasioned by the extremely low endogenous release of LH-RH at the mid-luteal period, as postulated previously¡(Wange/a/., 1976b); this in turn minimizes the self-priming effect of LH-RH and results in a reduction of activity of the first pool. When an adequate or excessive amount of LH-RH stimulation is provided, as in the case of prior priming by a 4-h LH-RH infusion, an extraordinary augmentation of the acutely releasable pool of LH is found which exceeds that observed in both the early and the late follicular phase of the cycle (Hoff et al, 1977). These findings provide strong support for our contention that (1) the mid-luteal levels of oestradiol and progesterone do not inhibit the pituitary response to LH-RH action but may in fact possess the potential to amplify first-pool activity by additional LH-RH.…”

“…During this phase of the cycle, the large second pool is maintained as in the late follicular phase, but the first pool is very much smaller (Hoff et al, 1977). This phenomenon is probably not due to an inhibitory effect of combined oestradiol and progesterone on LH-RH-mediated gonadotrophin release, but occasioned by the extremely low endogenous release of LH-RH at the mid-luteal period, as postulated previously¡(Wange/a/., 1976b); this in turn minimizes the self-priming effect of LH-RH and results in a reduction of activity of the first pool.…”

“…(2) Combined oestradiol and progesterone at mid-luteal levels apparently suppress endogenous LH-RH release more than does oestradiol alone. Recent evidence suggests a causal relationship between episodic LH-RH secretion and pulsatile LH release (Carmel, Araki & Ferin, 1976;Dowd, Barofsky, Chaudhuri, Lloyd & Weisz, 1975 In contrast to both the follicular and the luteal phase, there is an enormous increase in the firstpool activity at mid-cycle (Hoff et al, 1977), a situation also apparent in acyclic hypogonadal sub¬ jects (Moore & Price, 1932). Although the oestradiol levels are at the two extremes under these two conditions, the common denominator is an elevated hypothalamic LH-RH input to the gonado¬ tropi« (Ben-Jonathan, Mical & Porter, 1973;Carmel et al, 1976;Porter, Ben-Jonathan, Oliver, Eskay & Winter, 1976 (Leblanc, Lachelin, Abu-Fadil & Yen, 1976).…”

Ο ωοθηκικός έλεγχος της υποφυσιακής ευαισθησίας στη GnRH στις γυναίκες με PCOS

“…Από τέτοιες αρχικές µελέτες προέκυψαν οι παρατηρήσεις ότι ανεξάρτητα από τη χορήγηση της GnRH µε σταθερό ή κατά ώσεις τρόπο, η ποσότητα της LH που εκκρίνονταν εξαρτιόνταν ουσιαστικά από τη φάση του κύκλου στην οποία γίνονταν η εξωγενής χορήγηση (Wang et al, 1976;Hoff et al, 1977). Ως γνωστό, έχει θεωρηθεί ότι η αρχική, στα 30 min και η επακόλουθη απάντηση (δηλαδή η ποσότητα της ορµόνης που εκκρίνεται σε απάντηση σε επακόλουθες διεγέρσεις ή σε συνεχή έγχυση της GnRH) των γοναδοτρόφων στη GnRH αντιπροσωπεύουν την πρώτη-άµεσα εκκρινόµενη (ευαισθησία της υπόφυσης) και την δεύτερη-εφεδρική δεξαµενή αντίστοιχα (Wang et al, 1976).…”