PITUITARY AND OVARIAN HORMONAL RESPONSE TO 48 h GONADOTROPHIN RELEASING HORRMONE (GnRH) INFUSIONS IN FEMALE RHESUS MONKEYS

Abstract

The effects of prolonged gonadotrophin-releasing hormone (GnRH) infusions on LH, FSH, oestrogens and progesterone secretion were studied in female rhesus monkeys at various times of the menstrual cycle and after castration. GnRH was infused at the rate of 15 \g=m\g/h for 48 h. This resulted in mean peripheral GnRH levels of 398 \m=+-\ 31.5 pg/ml (\m=+-\se) as measured by radioimmunoassay. As expected the pattern of gonadotrophin responses to GnRH varied considerably with the phase of the menstrual cycle. The largest LH increase was seen during the late follicular phase (6-fold over baseline), with a 3-fold increase during the luteal phase and a 2-fold one during the early follicular phase and in the period following the LH surge. Significant FSH increases (4-fold) were seen only during the follicular phase. Oestrogens increased about 2-fold within 4 h of the start of the infusion during the early follicular phase. In the late follicular phase and during the LH surge, they declined within 24 and 1 h, respectively. Large progesterone increases were seen only during the luteal phase. Of special interest is the fact that the increase in gonadotrophin secretion could not be maintained for the entire duration of the experiment even though GnRH continued to be infused at rates sufficient to elicit initial increases of several fold over baseline. Gonadotrophin release declined 4\p=n-\28 h after the initial stimulation. A further decrease below pre-infusion

Effects of Short-Term Treatment with Gonadotropin-Releasing Hormone (GnRH) or Ethinyl Estradiol on the Pituitary Responsiveness to GnRH

“…It is probable that the dissimilarity of our results with those published by these authors depends upon both the dosage and duration of exogenous estrogen administered as well as the long-term endogenous ste roidal milieu of the patients studied. The deterioration of pituitary gonad otropin function observed in our patients following a rather short treatment course of GnRH confirms the results of numerous studies in experimental animals [7] and in humans [9,23,24] which suggest that prolonged treat-ment either with GnRH or with its long-acting analogues will initiate a significant decline of pituitary responsiveness to GnRH stimulation.…”

Luteinizing Hormone Secretion during Continuous or Pulsatile Infusion of Norepinephrine: Central Nervous System Desensitization to Constant Norepinephrine Input

“…In the brain-pituitary-ovarian axis, desensitization is the result o f prolonged stimulation of either the pituitary by luteinizing hormone-releasing hor mone (LHRH) [2, 6, 10, 23, 24] or the ovary by luteinizing hormone (LH) [3,4], Thus, in monkeys with hypothalamic lesions that eliminated endogenous release of LHRH and thus LH [2] or in intact monkeys [10], continuous infusion 1 This work was supported by NIH grants HD05577 and AMO6704.…”

Neuroendocrine Regulation of Pulsatile Luteinizing Hormone Release in the Rat

“…Within 2-3 days, constant infusion not only failed to re store sustained LH secretion but resulted in lesion-induced, low baseline LH levels [64], However, when LHRH was administered in a circhoral manner to mimic the LH and apparently the LHRH release process in this species, ele vated LH values were maintained for many days [9,57], This appeared not to be due to the quantity of LHRH given but to its manner of administration, i.e., as a pulsa tile signal [9], Ferin el at. [32] reported that in intact female monkeys continuous 48-hour infusions of LHRH caused initial increases in LH secretion but that this secretion declined 4-28 h after the onset of infusion at various stages of the menstrual cycle. Studies in intact rats have also shown that prolonged continuous exposure of the pitu itary gland to LHRH initially increased LH release, yet within a few hours LH secretion began to decline despite the continued presence of the releasing hormone [15.…”