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Title: The gonadotrophic control of ovarian follicle growth in the ewe
Author: Picton, Helen M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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The studies detailed in this thesis were designed to investigate the gonadotrophic control of ovarian follicular growth and development in the ewe. The differential actions of exogenous preparations of FSH and LH on follicle population dynamics, follicle diameter and steroid production were studied in Welsh Mountain ewes which had previously been rendered hypogonadotrophic through the chronic administration of the potent GnRH agonist Buserelin. A series of experiments (Chapter 4) were conducted to determine the effects of 5-6 weeks of chronic agonist administration on pituitary function, gonadotrophin secretion and follicle growth in the ewe during the breeding season. In summary the results indicate that chronic agonist treatment promptly produced a consistent and reversible hypogonadotrophic state by suppressing the peripheral FSH concentration by 40-60% and by the inhibiting the pulsatile release of LH. This was achieved though the desensitization and down-regulation of the pituitary gonadotroph receptors to endogenous GnRH. The suppression of gonadotrophin secretion was associated with the attentuation of follicle growth at a dimater of 2.5 mm. By eliminating the physiologically important influences of the hypothalamic-pituitary axis on ovarian function the GnRH agonist model, evaluated in chapter 4, provides a novel strategy for the investigation of the differential actions of pure preparations of FSH and LH in control of ovarian follicular function in otherwise intact and healthy animals. The function of the gonadotrophins in the process of folliculogenesis was assessed in agonist suppressed ewes by the continuous, intracenous infusion of different concentrations of FSH and LH pulses on follicle growth and function were assessed by comparing the number, size and in vitro steroidogenic capacity of follicles from agonist treated animals with similar parameters of follicle development measured in control ewes at different stages of the oestrous cycle (chapter 3). Interestingly the half-life of the exogenous infused gonadotrophin preparations was increased in the agonist treated animals (chapter 7). The results from the experiments detailed in chapters 5,6,8 and 9 suggest that the role of FSH- and in particular of LH- in the control of the terminal stages of follicular development in the ewe must be re-evaluated. FSH is clearly the key extra-gonadal hormone in the stimulation of folliculogenesis in the ewe as, in the presence of only basal concentrations of LH and in the absence of LH pulses, FSH can induce substantial preovulatory follicular development and oestrogen biosynthesis (chapters 5,6, and 9). Importantly the large follicles activated by FSH ovulate in response to hCG and produce CL with normal weight and progesterone production (chapter 6). The results from chapter 9 indicate that there is a threshold for the stimulation of follicle growth by FSH and upon reaching this threshold FSH readily induces preovulatory follicular development. Once the FSH concentration has reached the stimulatory range the subsequent duration of the FSH infusion influences the number of follicles which develop (chapter 6). These results suggest that the physiological determinant of the ovulation rate of the Welsh ewe is the systemic concentration of FSH in the 48-72h preceding luteal regression with selection of the ovulatory follicle occurring around 18-24h after luteolysis (chapter 3). The results of the infusion studies undoubtedly bring into question the long held views on the physiological importance of a pulsatile pattern of LH secretion in the process of folliculogenesis in the ewe. The findings of chapter 8 demonstrate that in the agonist model ewe there is an essential synergism between FSH and the tonic concentration of LH present throughout the infusion period in the promotion of follicular maturation and oestrogen biosynthesis. After immunoneutralization of the basal concentration of LH the infused FSH no longer stimulated normal levels of oestrogen production or follicle development beyond 2.0 mm diamter. Also, the infusion of large amplitude LH pulses antagonized the development of the provulatory follicles induced by FSH in the presence of basal concentrations of LH (chapters 5 and 8). It is hypothesized that the inhibitory effect of large amplitude LH pulses on the terminal stages of follicular development is mediated through the direct inhibition of FSH activated aromatase activity and/or through an enhanced thecal androgen production. These actions of LH drive unselected follicles towards atresia. As a result of these studies it is possible to hypothesize that the development of ovulatory follicles and the induction of follicle atresia is dependent on the delicately balanced interactions of FSH, LG and the follicular steroids. FSH is responsible for the stimulation of follicle growth and preovulatory maturation whereas LS, while tirggering the preovulatory gonadotrophin surge, also regulates ovulation rate through the induction of atresia in those follicles which are not destined to ovulate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available