Experimental Studies on the Endocrine Regulations During the Periovulatory Phase of the Human Menstrual Cycle

Abstract

In an attempt to simulate some parts of the progesterone and oestradiol patterns found in the normal menstrual cycle by intramuscular injections of microcrystalline progesterone and oestradiol benzoate, two distinct effects of progesterone and oestradiol on the hypothalamic cyclic centre were observed. Both progesterone and oestradiol can produce a positive feedback on the cyclic centre as measured by a plasma LH surge when administered to women with primary amenorrhoea, to castrated women, to women in the postmenopause and to eugonadal women receiving oral therapy of 60 μg of ethinyloestradiol per day. Subsequent LH peaks could be induced with progesterone or oestradiol benzoate after an oestradiol induced LH peak, but no further LH peak could be induced by either progesterone or oestradiol following a first progesterone induced LH peak. The progesterone induced LH discharge differed from that induced by oestradiol: It always occurred immediately after progesterone injection regardless of the dose given and was terminated very abruptly. The duration of the release of LH seems to decrease with an increase in the progesterone dose. In contrast, the first significant rise in the plasma LH concentration after oestradiol benzoate injection occurred after a latent phase of at least 24 hours. A significant FSH increase in the plasma was only seen following progesterone injection. The results of these feedback studies are interpreted in conjunction with the steroid pattern of the human female menstrual cycle. 17β-oestradiol was suggested as the initial triggering stimulus in the cycle leading to an LH surge. This first LH surge may cause the pre-ovulatory luteinization of the theca interna, thus, resulting in an increase of plasma progesterone. The biphasic stimulatory and inhibitory feedback effect of progesterone provides the final dosage regulation of the total LH discharge by regulating the amount of LH released in the second part of the biphasic midcycle peak. Progesterone also blocks the cyclic centre to further stimulation during the luteal phase of the cycle. The biphasic feedback effect of progesterone is interpreted as a possible periovulatory mechanism for mono-ovulation in the human female.

Actions of estradiol on discrete attributes of the luteinizing hormone pulse signal in man. Studies in postmenopausal women treated with pure estradiol.

“…This secondary recovery in LH pulse frequency was associated with a parallel increase in mean and integrated serum LH concentrations. The latter pattern resembles the so-called positive feedback effect of estradiol observed under physiological and various experimental conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). In particular, the present results are consistent with observations in the spontaneously cycling cow, sheep, and human, i.e., estimated LH pulse frequency increases in the late follicular phase as circulating concentrations of estrogenic and other hormones rise before the LH surge (12,33,34).…”

“…7 C). The significantly biphasic responses to estradiol observed here mimic in some respects the classical negative and positive feedback actions ofestradiol that are believed to be exerted during spontaneous normal menstrual cyclicity and occur in postmenopausal individuals in response to other modes of estrogen replacement (1)(2)(3)(4)(5)22). Thus, the present pharmacological model of estrogen action has permitted us to investigate the time-dependent and biphasic impact of estradiol on specific properties of spontaneous pulsatile LH release.…”

“…Investigations ofthe human menstrual cycle suggest that estradiol can exert both negative feedback (suppressive) and positive feedback (facilitative) effects on gonadotropin secretion (1)(2)(3)(4)(5). Moreover, studies in ovariectomized rodents and other mammals subjected to various regimens of sex-steroid hormone replacement have suggested possible actions of estradiol on the hypothalamic release of gonadotropin-releasing hormone (GnRH)' and on the responsiveness of gonadotrope cells to GnRH (6)(7)(8)(9)(10)(11)(12)(13).…”

Neue Erkenntnisse über die endokrine Regulation der Ovarialfunktion

“…Nach den beiden in Abbildung 12 dargestellten Experimenten liegt bei dieser Versuchsperson die Stimulierungsschwelle bei einer Plas maprogesteronkonzentration von < 2 ng/ml und die Hemmungs schwelle bei maximal 14 ng/ml. Bei einem anderen Experiment wurde nach Injektion von 50 mg Progesteron eine Terminierung des progeste roninduzierten LH-Gipfels bei einer Plasmaprogesteronkonzentration von maximal 8 ng/ml gefunden [26].…”

“…11). Nach einer Aktivie rung durch Progesteron ist das zyklische Sexualzentrum also gegenüber einer zweiten Aktivierung vorübergehend refraktär [23] [38] über eine konstante Zeit von zirka 46 h [26,38]. Der relative Dosis-und Zeitanteil beider LH-Gipfel an der gesamten LH-Aus schüttung ist variabel [38], In der schematischen Abbildung sind als Beispiele die Extremfälle mit relativ überwiegender LH-Sekretion im 2.…”