The dynamics of ovarian and pituitary hormone changes during the midcycle period were evaluated. Changes in hormone levels were determined at 2-h intervals for 5 consecutive days during the periovulatory phase of the cycle in five women. During the 50 h preceding the onset of the surge, the rates of increments for estradiol (E2), progesterone (P4), and LH were similar, with doubling times of 57-61 h. The onset of LH and FSH surges was found to occur abruptly (LH doubled within 2 h). They were temporally associated with the attainment of peak E2 levels and occurred 12 h after the initiation of a rapid rise of P4. The mean duration of the surge was 48 h, with a rapidly ascending limb (doubling time, 5.2 h) lasting 14 h accompanied by a rapid decline of E2 and a continued rise of P4. The surge was followed by a peak plateau of gonadotropin levels lasting for 14 h and a transient leveling of P4. The longer descending limb (half-time, 9.6 h), lasting for 20 h, was associated with a second rapid rise of P4, beginning 36 h after surge onset or 12 h before termination of the surge. By using the onset of the LH surge as a reference point, our data provide a relatively precise picture of the hormonal changes preceding the onset of the gonadotropin surge and the temporal relationship between the multiphasic P4 rise and pituitary-ovarian function.

To determine whether endogenous opiates exert an inhibitory action on LH secretion during the menstrual cycle, LH increments were examined in response to a specific opiate antagonist, naloxone, infused at 1.6 mg/hr for 4 hrs. Naloxone had no discernible effect on LH release during the early follicular phase. By contrast, a significant LH increment was observed in both the late follicular and mid-luteal phases of the cycle but the patterns of LH increment were distinct. Late follicular subjects exhibited slow, progressive increases in LH, while prompt, episodic and quantitatively greater LH increments were evident in mid-luteal phase subjects. These observations suggest that endogenous opiates are involved in the regulation of LH secretion during the high estrogen and estrogen-progesterone phases of the menstrual cycle.

The effect of acute activation of the ACTH-adrenal axis on circulating testosterone (T) levels was investigated. Elevation of circulating cortisol resulting from insulin-induced hypoglycemia or the administration of hydrocortisone was followed by a rapid decrease in serum T levels, without accompanying changes in LH or PRL. These findings suggest that hypercortisolism of endogenous or exogenous sources suppresses T secretion by a direct action on the testis. This adrenal-testicular axis may have biological implications on the reproductive adaptation to stress.

Administration of a dopamine (DA) antagonist, metoclopramide (MCP) resulted in dose-related acute increments of circulating levels of LH and FSH in patients with hyperprolactinemic anovulation due to pituitary microadenoma but not in normal cycling women during the early follicular phase. Concomitant PRL responses to MCP in hyperprolactinemic patients were 1/10 those observed in the cycling women. These findings suggest a relative DA excess at the hypothalamic LRF neurons and a relative DA deficiency at the adenoma lactotroph of hyperprolactinemic patients as compared to cycling women.

To test the postulate that endogenous opioid peptides may be involved in the neuroendocrine mechanisms controlling the frequency and amplitude of LH pulses, saline and an opioid receptor antagonist, naloxone, were infused sequentially, each for 6-h intervals, in six normal cycling women during the luteal phase of the menstrual cycle. During naloxone infusion (1.6 mg/h), there was a significant (P less than 0.01) increase in both the frequency and amplitude of LH pulses compared to those in saline controls. FSH pulses were not discernible in individual subjects; however, a significant increment in FSH levels occurred concomitantly with the increase in LH. These data strongly suggest that endogenous opiates, through an inhibition of hypothalamic LRF, participate in the endocrine events leading to the low frequency of episodic LH secretion characteristic of the luteal phase of the human menstrual cycle.