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2. ENDOCRINE CONTROL OF THE OESTROUS CYCLE
Introduction
2.1 The cyclic changes that occur in the female reproductive tract are initiated and regulated by the
hypothalamic-pituitary-ovarian (HPO) axis. Although folliculogenesis occurs independently of hormonal
stimulation up until the formation of early tertiary follicles, the gonadotrophins luteinising hormone (LH) and
follicle stimulating hormone (FSH) are essential for the completion of follicular maturation and development of
mature preovulatory (Graafian) follicles. The sites of production and key functions of the major reproductive
hormones in the female rat are summarised in Table 2.1.
Pituitary gonadotrophin secretion drives follicular maturation and oestrogen secretion
2.2 Levels of LH and FSH begin to increase just after dioestrus. Both hormones are secreted by the same
secretory cells (gonadotrophs) in the pars distalis of the anterior pituitary (adenohypophysis). FSH stimulates
development of the zona granulosa and triggers expression of LH receptors by granulosa cells. LH initiates the
synthesis and secretion of androstenedione and, to a lesser extent, testosterone by the theca interna; these
androgens are utilised by granulosa cells as substrates in the synthesis of oestrogen. Pituitary release of
gonadotrophins thus drives follicular maturation and secretion of oestrogen during prooestrus.
2.3 Gonadotrophin secretion by the anterior pituitary is regulated by luteinising hormone-releasing hormone
(LHRH), produced by the hypothalamus. LHRH is transported along the axons of hypothalamic neurones to
the median eminence where it is secreted into the hypothalamic-hypophyseal portal system and transported to
the anterior pituitary. The hypothalamus secretes LHRH in rhythmic pulses; this pulsatility is essential for the
normal activation of gonadotrophs and subsequent release of LH and FSH.
Ovulation is triggered by an oestrogen-mediated preovulatory LH surge
2.4 The increase in oestrogen observed during prooestrus initiates several characteristic morphological
changes in the uterus and vagina (Table 2.1). This rise in oestrogen also suppresses release of LHRH by the
hypothalamus, as well as directly inhibiting pituitary secretion of both LH and FSH. Negative feedback control
of pituitary FSH secretion is also achieved by the peptide inhibin, produced by the granulosa cells of the
maturing follicle. The various hormonal interactions of the HPO axis are summarised in Figure 2.1 below.
2.5 Oestrogen levels rise during the morning, peak around midday and then fall during the afternoon of
prooestrus. Once peak oestrogen levels are reached its inhibition of LHRH and gonadotrophin secretion ceases.
At this point, oestrogen starts promoting both hypothalamic LHRH release and anterior pituitary
responsiveness to LHRH. This positive oestrogenic modulation of hypothalamic-pituitary function results in a
preovulatory LHRH surge and corresponding surge in LH.
2.6 The LH surge, which closely follows the oestrogen peak, occurs during the afternoon of prooestrus and
triggers ovulation approximately 10-12 hours later. FSH levels peak twice in the rat; the first (preovulatory)
peak is LHRH-dependent and occurs in concert with the LH peak. This is followed by a second (postovulatory)
rise in FSH that occurs at the time of ovulation or shortly after. This secondary FSH elevation is thought to be
LHRH-independent, reflecting reduced inhibin synthesis by the postovulatory follicle.
