title: The effect of purified gonadotrophins on the ovarian structure
Creators: name: El-Tomi, Nabil Fouad
Publisher: name: University of Glasgow
Year: 1979
Subjects: subject: Endocrinology.

description: Mature female Sprague-Dawley rats were hypophysectomized towards the end of oestrus as indicated by daily vaginal smears. All animals exhibited regular four-day cycles. At the seventh day after hypophysectomy, all ovarian structures had atrophied leaving small pre-antral follicles and apparently healthy looking corpora lutea. Apart from intact and hypophysectomized animals which were used as controls, the hypophysectomized animals were divided into three main groups: Group I were given increasing doses of a highly purified FSH preparation. Group II were given increasing doses of a highly purified LH preparation. Group III were given the minimal effective dose of FSH and increasing doses of a highly purified LH preparation. All hormone injections were given as a single sub-cutaneous injection on the seventh day after hypophysectomy. By this time the only normal structures in the ovaries of the experimental animals were corpora lutea and very small pre-antral follicles. Graafian follicles had either disappeared or were in the advanced stages of atresia. The interstitial tissue was inactive and showed marked fatty change. The administration of FSH was followed by changes suggesting reactivation of the corpora lutea - accumulation of cytoplasmic RNA and an increase in 33 steroid dehydrogenase activity. Following this, follicular growth occurred and the interstitial cells lost their degenerate appearance but showed no sign of luteinization. Antral follicles were produced and the thecal cells made their appearance. The latter also did not luteinize. From these results it is argued that FSH stimulates the corpus luteum to produce the oestrogen necessary to initiate the first stages of follicular growth and stimulate the production of FSH receptors in granulosa cells. Although thecal cells were formed and the interstitial tissue became healthy in appearance there was no evidence of excessive androgen production. It was deduced from this that the unluteinized spindle-shaped thecal cells and the similarly unluteinized interstitial, cells were a morphological form which may be mainly associated with oestrogen production. LH caused hyperaemia and some increase in the size of the corpora lutea. There were also indications of increased functional activity as with FSH. Interstitial tissue was "repaired" and showed signs of partial luteinization. Although it is known that LH stimulates the production of oestrogen in hypophysectomized rats provided corpora lutea are present in the ovaries there was no evidence of folliculogenesis. Indeed the process of atresia appeared to be hastened. It is suggested that the absence of follicular growth was due to the production of androgens by the stimulated interstitial cells. From this it was concluded that the occurrence of luteinization in these cells was an indication of a high production rate of androgens. FSH and LH administered together restored the ovarian structure to a reasonably normal condition. Folliculogenesis was active and the interstitial tissue became active in appearance. The corpora lutea, obviously pre-existing, were much enlarged and active. These changes were within the range of normality provided the dose of LH remained small. With increasing doses of LH the theca and the interstitial tissue became hyperplastic and fully luteinized. Granulosa cell growth ceased and ultimately the granulosa cells disappeared leaving theca lutein cysts. These results seemed to indicate that the main action of these larger doses of LH was on the thecal and the interstitial cells, resulting in the production of large quantities of androgen which counteracted the folliculogenic activity of the small dose of FSH. They help to support the hypothesis suggested as an 20 explanation for the results of the experiments with LH alone. An analogy is drawn to the polycystic ovarian syndrome in humans. From the above results a further hypothesis is put forward to provide one reason for the increase in FSH at the time of the ovulation surge of LH. It is suggested that the increase in FSH acts to protect the granulosa cells from the atretic action of androgens produced under the influence of LH, by converting the androgens to progesterone.