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Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sexdependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2a(orl6a)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This rmding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH.Episodic secretion is a general characteristic of many hormones, including pituitary-dependent hormones, pancreatic islet, and parathyroid hormones (1), and is often crucial to the triggering of hormone-dependent responses in target cells. For growth hormone (GH), secretion by the pituitary is not only intermittent, or pulsatile, but also the frequency of pulsation is sex-dependent. In many species, including the rat, chicken, and human (2-5), pituitary GH secretion is more frequent in females than in males. In the case of the female rat, a high pulse frequency results in GH present in circulation continuously, at levels 2 10-20 ng/ml of plasma. This situation contrasts with the intermittent presence of GH in plasma of male rats (2, 6). Studies in rats (7-10) and mice (11-13) have demonstrated that the expression of a number of sexually differentiated hepatic proteins, including cytochrome P450 (P450)-linked steroid hydroxylases and drugmetabolizing enzymes, is primarily determined by plasma GH profiles and only secondarily regulated by the gonadal hormones through their effects on the hypothalamo-pituitary axis and its control of GH secretion (14-16).The plasma GH profile in a male rat is characterized by a pulse of 200-250 ng of GH per ml every 3-4 hr followed by a 2-to 2.5-hr period when circulating GH is nearly undetectable (.2 nrg/ml). It is unclear, however, just what features in this pattern are recognized as male by the hepatocyte. This critical question is addressed by the present study, which uses a recently developed external pump apparatus (17) for generation of periodic GH pulses of various frequenc...

There is evidence that the mammalian female genital tract is capable of responding immunologically when challenged with alloantigens. The antigenic properties of male gametes have been well delineated. However, it is only rarely that a female mammal ever responds immunologically to the male gametic antigens as a result of coitus. When a proposed mechanism of suppression of antigenicity of epididymal spermatozoa was tested experimentally, the results indicated that two proteins (uteroglobin and transglutaminase) present in the prostate may be responsible for suppressing sperm antigenicity in the rabbit.

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Hypophysectomy resulted in a total elimination of measurable circulating growth hormone with an associated loss of body weight gain. The typical sexually dimorphic plasma growth hormone patterns: pulsatile profiles in male rats and tonic-like secretion in female rats, were lost. The male-and female-dependent profiles of plasma growth hormone, monitored from serial blood collections, were restored by administering the hormone through a single electrically controlled external pump attached to an indwelling catheter, and by implanting osmotic pumps intraperitoneally, respectively. Restoring the natural patterns of plasma growth hormone in animals devoid of pituitaries, re-initiated body growth. However, the body weight gains in both sexes of hypophysectomized rats were much greater when rat growth hormone was introduced to the animals in a masculine (pulsatile) pattern that appeared to be independent of pulse frequency, rather than in a continuous feminine profile. Subcutaneous injections, the most commonly reported method of administration, produced low-amplitude, long-lasting plasma peaks that were not as effective as pulse infusion in restoring growth. The procedure allows manipulation of the hormone profile (i.e. number of pulses/day, pulse amplitude, and through duration in the pulsatile pattern, and plasma concentration in the tonic pattern) in order to identify, and thus study the presumed salient components of the pattern regulating growth hormone responses.