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U.S. Department of Agriculture: Agricultural Publications from USDA-ARS / UNL Faculty Research Service, Lincoln, Nebraska

1982

Hormonal Interrelationships Between , Pituitary and Testis of Rams and Bulls

Bruce D. Schanbacher USDA-ARS

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Schanbacher, Bruce D., "Hormonal Interrelationships Between Hypothalamus, Pituitary and Testis of Rams and Bulls" (1982). Publications from USDA-ARS / UNL Faculty. 763. https://digitalcommons.unl.edu/usdaarsfacpub/763

This Article is brought to you for free and open access by the U.S. Department of Agriculture: Agricultural Research Service, Lincoln, Nebraska at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Publications from USDA-ARS / UNL Faculty by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Journal of Animal Science 55 (1982), pp. 56-67.

Hormonal Interrelationships Between Hypothalamus, Pituitary and Testis of Rams and Bulls

Bruce D. Schanbacher1

US Department of Agriculture2, Clay Center, NE 68933

Summary Introduction This mini-review aims to summarize some of Despite the need for efficient our recent findings relating to testicular func• by males and the important contribution males tion and feedback control of the hypothalamic- make to propagation of the species, limited pituitary axis by testicular steroids in rams and information has been accumulated on the basic bulls. secretion in intact males is physiological mechanisms that regulate repro• not tonic, but is characterized by episodic ductive processes in males. This is true for pulses. This pattern of secretion is dictated by domestic species, particularly rams and bulls. inputs of the central via secre• Livestock production contributes substantially tions of the hypothalamus (luteinizing hor• to the economic stability of agriculture in this mone-releasing ; LHRH) and anterior country; therefore, a better understanding of pituitary (; LH). A tem• those factors contributing to the reproductive poral relationship exists between concentra• success or failure in these species is warranted. tions of LH and testosterone in serum and A number of reproductive characteristics are evidence is presented that strongly suggests that quantifiable in males, however, it seems that their episodic secretion is dependent on discrete the testes should be of paramount importance. episodes of LHRH discharge from the hypo• Two major functions of the testis include . Based on data from experiments with biosynthesis by the interstitial cells rams and bulls, I suggest that acutely castrated and production within the seminiferous males (but not chronic castrates) remain sus• tubules. Although these two functions are ceptible to the effects of segregated anatomically, intercellular communi• testosterone, i.e., LH concentrations remain cation exists between them. Recent reviews suppressed in serum of animals given testos• have been prepared on quantitiative aspects of terone replacement therapy immediately fol• (Amann, 1981) and regulation lowing castration. -17j3, on the other of the hypothalamic-pituitary seminiferous hand, abolishes pulsatile LH release and sup• tubule axis by inhibin (Setchell et al, 1977). presses mean LH concentrations in both acute Therefore, this paper will review our current and chronic castrates. Therefore, testosterone understanding of testosterone secretion and the feedback on LH secretion may, in part, involve hypothalamic-pituitary- axis in rams extragonadal conversion to estradiol-17j3 to and bulls. block pulsatile LHRH release. The potent inhibitory effects of estradiol on LH secretion provide an experimental probe for future in• Hypothalamic-Pituitary-Gonadal vestigations relating to mechanisms controlling Axis male reproduction. The anterior pituitary through its secretion of the , luteinizing hormone (LH) (Key Words; Hypothalamus, Pituitary, Testicu• and follicle stimulating hormone (FSH) partic• lar Steroids, Negative Feedback.) ipate in regulation of testicular function. The anterior pituitary, itself, is regulated by inputs from the central nervous system, which are 'The author acknowledges the cooperation of the coordinated via the hypothalamic secretion of Nebraska Agr. Exp. Sta., Univ. of Nebraska, Lincoln, luteinizing hormone releasing hormone (LHRH; and the assistance of Michael J. D'Occhio, James E. Kinder and Cindy Rainbolt in obtaining some of the also referred to as GnRH). The interrelation• original data cited. Appreciation is extended to Kathy ships of hypothalamus, pituitary and testis are Leising for typing the manuscript. schematically presented in figure 1. 2 Roman L. Hruska U.S. Meat Animal Research Center, Agr. Res. Ser. Testicular steroidogenesis depends on con-

56 AND REGULATION OF TESTICULAR FUNCTION 57 tinuous support from the pituitary in the form of LH. This binds to specific receptors on the plasma membrane of Leydig cells to activate adenyl cyclase. This enzyme catalyzes the conversion of ATP to cAMP, which serves as a second messenger to activate a cytoplasmic protein kinease that is responsi• ble for the conversion of cholesterol to sex steroids, primarily testosterone (Neaves, 1975). The remainder of this report will deal with the interrelationships between inputs of the hypo• thalamus (i.e., LHRH), LH secretion and feed• back control of the hypothalamic-pituitary axis by testicular steroids.

Hypothalamic Control of Testosterone Secretion Testosterone secretion in intact males is not tonic, but is characterized by episodic pulses. This pattern of secretion varies from one ani• mal to the next and is probably a function of age, reproductive status, health, external en• vironment and other unidentified factors (Schanbacher and Ford, 1977; Lincoln, 1978; Lacroix and Pelletier, 1979a,b; Schanbacher, 1980a). Diurnal rhythms in serum testosterone are not evident in rams or bulls (Falvo et al., Figure 1. Hypothalamic-pituitary control of tes• ticular function. Gonadotropin releasing hormone 1975). (GnRH) from the hypothalamus mediates pituitary Several investigators have reported a tem• release of LH and FSH, which in turn binds to specific poral relationship between secretory episodes membrane receptors on Leydig cells and Sertoli cells, of LH and testosterone with a lag period of respectively. Testicular secretions (testosterone and estradiol from Leydig cells and inhibin from Sertoli approximately 60 min between peak concen• cells) act on the brain and anterior pituitary, where trations (Katongole et al., 1971, 1974;Sanford they exert control of gonadotropin release via negative et al., 1974; Schanbacher and Ford, 1976; feedback mechanisms. Testosterone also facilitates Lincoln et al., 1977; Schams et al., 1978; spermatogenesis by binding to cytoplasmic receptors D'Occhio et al., 1982b). The ability of iv injec• in the Sertoli cells of the seminiferous tubules. tions of either LH or LHRH to induce normal surges of testosterone in serum (Thibier, 1976; Schanbacher and Echternkamp, 1978; Schan• (Fink and Jamieson, 1976) varies in a pulsatile bacher, 1979a, 1980b) has provided supplemen• manner. tary evidence that pulsatile testosterone secre• Lincoln and Frazer (1979) studied the im• tion is the result of a pulsatile pattern of LHRH portance of neural inputs from the hypothala• secretion from the hypothalamus. Further evi• mus indirectly by neutralizing LHRH secretion dence for this conclusion is illustrated in figure with LHRH antibodies. Passive immunization 2, wherein striking similarity exists for the of intact Soay rams with LHRH antiserum re• naturally occurring LH-testosterone episode ob• sulted in an immediate blockage of the episo• served in an intact bull (figure 2A) and the LH- dic fluctuations of both LH and testosterone. testosterone episodes that have been induced Similar observations have been made for ram by an injection of synthetic LHRH (figure 2B). lambs (Schanbacher, 1982) and for bull calves Based on these data I suggest that an intermit• (B. D. Schanbacher, unpublished data) follow• tent pattern of LH secretion is dictated by a ing active immunization against LHRH. Failure similar pattern of LHRH secretion by the hypo• of these lambs and calves to respond to exogen• thalamus. Indeed, LHRH concentrations in ous LHRH showed that LHRH immunoneutral- blood taken from pituitary portal vessels of ization provides a physiological block to the rhesus monkeys (Carmel et al., 1976) and rats hypothalamic-pituitary-Leydig cell axis. Data 58 SCHANBACHER

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• • ' * * ' i 0600 1000 1400 1800 TIME OF DAY (h) Figure 2. Luteinizing hormone (o) and testosterone (•) concentrations in serum of a mature bull during a 14-h intensive bleeding period (A) and another mature bull injected iv every 4 h with 1,000 ng of LHRH (B). (From Schanbacher and D'Occhio, 1982).

that illustrate the biological consequences of concentrations of LH and testosterone and pro• LHRH immunization in lambs are presented in vide evidence that their episodic secretion is table 1. Note the marked reduction in testicu• dependent on secretory episodes of LHRH lar weight, the low to nondetectable concentra• from the hypothalamus. tions of LH, FSH and testosterone in serum and the lack of LH release in response to exogenous Regulation of LH Secretion LHRH. by Testosterone The above results clearly demonstrate the Luteinizing hormone is the principal regula• temporal relationship that exists between serum tor of testicular steroidogenesis; however, the

TABLE 1. PAIRED TESTES WEIGHTS AND CONCENTRATIONS OF LH, FSH AND TESTOSTERONE IN SERUM OF RAM LAMBS IMMUNIZED AGAINST LUTEINIZING HORMONE RELEASING HORMONE (LHRH) OR BOVINE SERUM ALBUMIN (BSA)a

Serum LH Serum Paired response to testes weight, LH, FSH, Testosterone, 250 ng LHRH, g ng/ml ng/ml ng/ml ng/ml

342 ± 21 2.0 ± .2 101 ± 9 2.4 ± .5 8.5 ± 1.1 318 t 21 2.1 t .02 81 ± 10 2.3 ± .3 8.1 ± 1.6 68 + 26** .6 ± .04** 56+ 3** .3 ± .1** .2 ± .1** 12.8 + 2.7** 376 ± 28** .3 ± .1** 13.4 ± 2.3**

aValues are means ± SE. "Different from intact group (P<.01). ENDOCRINOLOGY AND REGULATION OF TESTICULAR FUNCTION 59

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0800 1000 1200 I4O0 1600 1800 2000 2200 2400 0200 0400 0600 0800 TIME OF DAY (h) Figure 3. Luteinizing hormone (•) and testosterone (o) profiles in serum of two wethers bled at 10-min intervals for 24 h, 6 wk after castration. (From D'Oechio et al., 1982b.)

amount of LH required to maintain adequate implanted with Silastic capsules containing serum testosterone is less than the animal is testosterone are shown in figure 5. The im• capable of secreting (Neaves, 1975). Feedback plants not only provided normal physiological inhibition by gonadal steroids forms an inte• concentrations of testosterone in blood (2.01 gral part of the hypothalamic-pituitary-testicu- ± .09 vs 2.25 ± .49 ng/ml of serum for im• lar axis in males (Lipsett, 1979; Schanbacher, planted castrate and intact control rams, respec• 1980c; Santen, 1981) and provides a plausible tively), but suppressed mean serum LH concen• explanation for the major differences in LH trations (2.2 ± .8 ng/ml) to those values ob• secretory patterns between castrate and intact served in intact rams (2.1 ± .2 ng/ml). In spite males. Because testosterone is quantitatively of these similarities, testosterone implanted the most important hormone secreted by the castrates, like intact rams, were variable with testis (Ewing and Brown, 1977), it seems rea• regard to number of LH secretory episodes sonable to assume that this steroid is largely exhibited per 24 h. These data indicate that responsible for the pattern of LH secretion in testosterone is the testicular steroid responsible intact males. This hypothesis was recently for feedback regulation of LH secretion in tested by monitoring the LH secretory pattern rams. of intact rams and comparing them with those of castrate rams given testosterone replacement therapy (D'Oechio et al., 1982b). Castrate ani• Regulation of LH Secretion by Androgenic mals showed frequent, rhythmic pulses of LH and Estrogenic Metabolites (figure 3), whereas intact animals showed infre• of Testosterone quent pulses of LH that occurred episodically Testosterone may be the secretory product (figure 4). These profiles are similar to those of the testis responsible for feedback regulation reported previously for castrate (Riggs and Mal- of LH secretion, but systemically and (or) cen• ven, 1974) and intact rams (Katongole et al., trally produced androgenic and estrogenic 1974; Sanford et al., 1974; Galloway and Pelle- metabolites may mediate the suppressive effects tier, 1975; Schanbacher and Ford, 1976; Lin• of testosterone on LH (Baird et al., 1968; coln, 1976). Secretory profiles for castrate rams Santen, 1981). Enzymes that metabolize testos- 60 SCHANBACHER

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0800 1000 1200 1400 1600 1800 2000 2200 2400 0200 0400 0600 0800 TIME OF DAY (h)

Figure 4. Luteinizing hormone (•) and testosterone (o) profiles in serum of three rams bled at 10-min inter• vals for 24 h. (From D'Occhio et al., 1982b.)

terone to Sa-reduced and aromatized steroids ity of LH secretion to 5a-reduced (figure 6) are present in the brain of males in and . Conclusions from studies with areas that are associated with gonadotropin these species indicate that both 5a-dihydro- secretion (Naftolin et al., 1975; Callard et al., testosterone and estradiol-17/3 are potent inhib• 1978). Furthermore, these same areas contain itors of LH secretion. Studies in sheep (Schan• specific receptors that bind androgens and bacher and Ford, 1977; Parrott and Davies, estrogens with high affinity (MacLusky and 1979) and cattle (D'Occhio et al., 1982a) have Clark, 1980;McEwen, 1980). shown a potent, inhibitory effect of estradiol- Several studies have been conducted using 17/3, but have left some uncertainty regarding rats (Swerdloff et al., 1972; Eldridge and the proposed role of 5a-dihydrotestosterone. Mahesh, 1974) or humans (Santen, 1975; A recent study with steers (D'Occhio et al., Winters et al., 1979a,b) to test the susceptibil• 1982a) demonstrated the importance of estra- ENDOCRINOLOGY AND REGULATION OF TESTICULAR FUNCTION 61

diol-17/3 as a regulator of LH secretion. Angus diol-17/3 abolished pulsatile LH release and calves that had been castrated at birth were in• suppressed mean LH concentrations in these fused with one-of-four different steriods at animals (figure 8). Steers infused with estradiol- approximately 10 mo of age. Each steroid was 17/3 released LH normally in response to an iv infused at a rate that would cause a blood injection of LHRH. Thus, LH release was prob• concentration equal or exceeding levels nor• ably blocked at the level of the hypothalamus mally associated with intact bulls. Neither and not the pituitary per se. Although the ques• testosterone, 5a-dihydrotestosterone nor tion arises from this study as to whether long- estrone affected the LH secretory profiles of term castrates are suitable models for the study these steers (figure 7). Secretion of LH con• of acute androgen feedback (McCarthy and tinued in the pulsatile manner characteristic of Swanson, 1976; Resko et al., 1977; Schan• long-term castrates. On the other hand, estra- bacher, 1981a), negative feedback by estradiol- 17/3 has been demonstrated in castrate males of other farm animal species (Parrott and OH Davies, 1979). Data presented above are con• sistent with the view that in the male bovine, estradiol-17/3 exerts negative feedback at the level of the hypothalamus to block pulsatile LHRH release.

Estradiol-17/3: in the Male Bovine 5a-reducta3e Aromofase Initiation of spermatogenesis and sexual maturation (i.e., puberty) in bulls is a slow developmental process associated with in• creasing concentrations of LH, FSH and testo• sterone in blood (Karg et al., 1976; Schams et al., 1978; Schanbacher, 1979b). Important 5*-Dhydrotestosterone Estradiol -17/3 interactions exist between pituitary sensitivity Figure 6. Metabolic conversion of testosterone to to LHRH and gonadal steroid feedback (Odell 5a-dihydrotestosterone and estradiol-17(3. et al., 1970; Mongkonpunya et al., 1975; 62 SCHANBACHER

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TIME OF DAY (h) Figure 7. Representative LH profiles for chronic castrate steers infused iv for 12 h with vehicle, estrone, 5a-dihydrotestosteronc and testosterone. Pituitary lesponsc to LHRH (1.000 ng iv) was determined at the end of the infusion period (•). (From D'Oechio et al., 1982a.) ENDOCRINOLOGY AND REGULATION OF TESTICULAR FUNCTION 63

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TIME OF DAY (h) Figure 8. Profiles of LH secretion in five chronic castrate steers infused iv for 12 h with estradiol-17/3. Pitui• tary response to LHRH (1,000 ng iv) was determined at the end of the infusion period (•). (From D'Occhio et al., 1982a.) 64 SCHANBACHER

during the prepubertal-pubertal period (Mong- konpunya et al, 1975; Tannen and Convey, 1977; Kesler and Garverick, 1977; Chantara- prateep and Thibier, 1979), an increase in episodic LH activity may be responsible for the testicular development that then initiates pu• berty (Lacroix and Pelletier, 1979a,b). From these results and the assumption that episodic LH release is the result of an episodic pattern of LHRH release from the hypothalamus, it can be hypothesized that endocrine events associated with puberty in bulls are initiated at the level of the central nervous system. Recently, a limited number of experiments were conducted to test the above hypothesis and determine the importance of episodic LH activity during pubertal development in beef bulls. Young bulls were implanted with estra•

_i 1 , 1 1 1 f 1 diol- 17(3 at dosages known to knhibit hypo• 26 30 34 38 40 42 44 thalamic LHRH activity and episodic LH re• AGE (wks) lease (Schanbacher, 1981b). Figure 9 shows the Figure 9. Changes in testicular diameter in young effectiveness by which this treatment delays bull calves implanted with estradiol-17(3 at 26 wk of testicular growth and also suggests that the age. Note the rapid testicular growth immediately fol• lowing implant removal. inhibitory effects of estradiol are acute because implant removal results in the immediate restor• Lacroix and Pelletier, 1979a; Schanbacher, ation of testicular growth. This growth is 1981b) to determine age at puberty. Although temporally associated with increased episodic controversy persists regarding the ability of LH activity (Schanbacher, 1981b). young bulls to respond to exogenous LHRH To ensure that the inhibitory effects of

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0600 1200 1800 1200 1800 1200 1800 TIME OF DAY(h) Figure 10. Serum LH (•) and testosterone (—) profiles in three bull calves implanted with estradiol-17|3 immediately before (left panel), 4 wk (middle panel) and 8 wk (right panel) after continuous pulsatile infusion of LHRH (500 ng/h iv). The calves were 34, 38 and 42 wk of age during the three sampling periods. (From Schanbacher et al., 1982.) ENDOCRINOLOGY AND REGULATION OF TESTICULAR FUNCTION 65

TABLE 2. PAIRED TESTES WEIGHT AND TOTAL DAILY SPERM PRODUCTION (TDSP) IN CONTROL BULLS, ESTRADIOL-IMPLANTED BULLS AND ESTRADIOL-IMPLANTED BULLS INFUSED HOURLY WITH 500 NG OF LUTEINIZING HORMONE RELEASING HORMONE (LHRH)3

Paired Total daily testes weigh t, sperm production. Treatment o X 10'

Control bulls 352 ± 26b 3.3 ± .9b Estradiol-implanted bulls 105 ± 14c 0 C Estradiol-implanted bulls, LHRH-infused bulls 254 i 12<1 1.2 ± ,3

Values are means ± SE for three calves 10 mo of age. ,,c'^Means within column without a common superscript differ (P<.05).

estradiol were at the hypothalamic level and the hypothalamus, pituitary and testis of rams not at the level of the pituitary and (or) testes, and bulls. The testicular responses to exogenous a second experiment (Schanbacher et al., 1982) LHRH and biological consequences of LHRH was conducted whereby calves implanted with immunoneutralization suggest that the hypo• estradiol were administered exogenous LHRH thalamus is primarily responsible for normal intermittently for a period of 8 wk. Figure 10 testicular function. The endocrine and exocrine shows the endocrine profiles for three im• functions of the testis appear to be regulated planted calves immediately before (left panel), by steroid feedback inhibition of gonadotropin 4 wk after (middle panel) and 8 wk after (right secretion at both hypothalamic and pituitary panel) hourly pulsatile injection of 500 ng of levels. LHRH. As in the first experiment, episodic LH activity was not apparent in calves implanted Literature Cited with estradiol. However, pulse infusion of LHRH in these calves resulted in a rhythmic, Amann, R. P. 1981. A critical review of methods for evaluation of spermatogenesis from seminal charac• pulsatile secretory pattern for LH. The secre• teristics. J. Androl. 2:37. tory profiles of LH and testosterone were simi• Baird, D., R. Horton, L. Longcope and J. F. Tait. lar after 4 and 8 wk of LHRH treatment with 1968. Steroid prehormones. Perspect. Biol. Med. mean serum concentrations increased over 11:384. those of estradiol-implanted, saline-infused con• Callard, G. V., Z. Petro and K. J. Ryan. 1978. Conver• sion of androgen to and other steroids in trol calves (LH:3.4 vs 1.8 ng/ml; testosterone: the vertebrate brain. Amer. Zool. 18:511. 13.0 vs .3 ng/ml). The effects of estradiol and Carmel, P. W., S. Araki and M. Ferin. 1976. Pituitary saline or LHRH treatment on testes weight and stalk portal blood collection in rhesus monkeys: total daily sperm production are shown in table Evidence for pulsatile release of gonadotropin 2. Not only did estradiol treatment restrict releasing hormone (GnRH). Endocrinology 99: 243. testicular growth, but sperm production was Chantaraprateep, P. and M. Thibier, 1979. LH and tes• not evident. Pulsatile administration of LHRH tosterone responses to gonadoliberin (LRH) treat• resulted in episodic LH release, enhanced ment in young bulls prior to and during puberty. testosterone secretion and initiation of sperma• Ann. Biol. Anim. Biochem. Biophys. 19:637. togenesis in bull calves treated with estradiol. D'Occhio, M. J., J. E. Kinder and B. D. Schanbacher. 1982a. Patterns of LH secretion in castrated bulls Therefore, hypothalamic inputs appear neces• (steers) during intravenous infusion of androgenic sary for the occurrence of endocrine events and estrogenic steroids: Pituitary response to exo• associated with puberty in bull calves. Sec• genous luteinizing hormone releasing hormone. ondly, estradiol implants provide an experi• Biol. Reprod. 26:249. mental probe for future investigations aimed at D'Occhio, M. J,, B. D. Schanbacher and J, E. Kinder. 1982b. Relationship between serum testosterone understanding the mechanisms controlling re• concentration and patterns of LH secretion in male production in males. sheep. Endocrinology 110:1547. Eldridge, J. C. and V. B. Mahesh. 1974. Pituitary- This review describes the close temporal gonadal axis before puberty: Evaluation of testicu• relationship that exists between secretions of lar steroids in the male rat. Biol. Reprod. 11:385. 66 SCHANBACHER

Ewing, L. L. and B. L. Brown. 1977. Testicular Press. New York. steroidogenesis. In: A. D. Johnson and W. R. McCarthy, M. S. and L. V. Swanson. 1976. Serum LH Gomes (Ed.) The Testis, Vol. 4. pp 239-275. concentration following castration, steroid hor• Academic Press, New York. mone and gonadotropin releasing hormone treat• Falvo, R. E,, A. E. Buhl, T. J. Reimers, G. R. Fox- ment in the male bovine. J. Anim. Sci. 43:151. croft, M. Hunzicker Dunn and P. Dziuk. 1975. McEwen, B. S. 1980. Gonadal steroids: Humoral mod• Diurnal fluctuations of testosterone and LH in the ulators of nerve-cell function. Mol. Cell. Endo• ram: Effect of HCG and gonadotrophin-releasing crinol. 18:151. hormone. J. Reprod. Fertil. 42:503. Mongkonpunya, K., H. D. Hafs, E. M. Convey, H. A. Fink, G. and M. G. Jamieson. 1976. Immunoreactive Tucker and W. D. Oxender. 1975. Serum luteini• luteinizing hormone releasing factor in rat pitui• zing hormone, testosterone and androstenedione in tary stalk blood: Effects of electrical stimulation pubertal and prepubertal bulls after gonadotropin of the medial . J. Endocrinol. 68:71. releasing hormone. J. Anim. Sci. 40:682. Galloway, D. B. and J. Pelletier. 1975. Luteinizing Naftolin, F., K. J. Ryan, I. J. Davies, V. V. Reddy, hormone release in entire and castrated rams fol• F. Flores, Z. Petro, M. Kuhn, R. J. White, Y. lowing injection of synthetic luteinizing hormone Takaoka and L. Wolin. 1975. The formation of releasing hormone, and effect of testosterone pro• estrogens by central neuroendocrine tissues. Rec. pionate pre-treatment. J. Endocrinol. 64:7. Prog. Horm. Res. 31:295. Karg, H., T. Giminez, M. HartI, B. Hoffmann, E. Neaves, W. B. 1975. Leydig cells. Contraception 11: Schallenberger and D. Schams. 1976. Testosterone, 571. luteinizing hormone (L1I) and follicle stimulating Odell, W. D., M. A. Hescox and C. A. Kiddy. 1970. hormone (FSH) in peripheral plasma of bulls: Studies of hypothalamic-pituitary-gonadal inter• Levels from birth through puberty and short term relations in prepubertal cattle. In: W. R. Butt, A. variations. Zentbl. Vet. Med. A. 23:793. C. Crooke and M. Ryle (Eds.) Gonadotrophins and Katongole. C. B„ F. Naftolin and R. V. Short. 1971. Ovarian Development, pp 371-385. Edinburgh: Relationship between blood levels of luteinizing E. and S. Livingstone. hormone and testosterone in bulls, and the effects Parrott, R. F. and R. V. Davies. 1979. Serum gonado• of sexual stimulation. J. Endocrinol. 50:457. tropin levels in prepubertally castrated male sheep Katongole, C. B., F. Naftolin and R. V. Short. 1974. treated for long periods with propionated testos• Seasonal variations in blood luteinizing hormone terone, dihydrotestosterone, 19-hydroxytestoster- and testosterone levels in rams. J. Endocrinol. 60: one or oestradiol. J. Reprod. Fertil. 56:543. 101. Resko, J. A., S. K. Quadri and H. G. Spies. 1977. Kesler, D. J. and H. A. Garverick. 1977. Luteinizing Negative feedback control of gonadotropins in hormone and testosterone concentrations in male rhesus monkeys: Effects of time after castra• plasma of bull calves treated with gonadotropin tion and interactions of testosterone and estradiol- releasing hormone. J. Dairy Sci. 60:632. 17/3. Endocrinology 101:215. Lacroix, A. and J. Pelletier. 1979a. Short-term varia• Riggs, B. L. and P. V, Malven. 1974. Spontaneous pat• tions in plasma LH and testosterone in bull calves terns of LH release in castrated male sheep and the from birth to 1 year of age. J. Reprod. Fertil. 55: effects of exogenous estradiol. J. Anim. Sci. 38: 81. 1239. Lacroix, A. and J. Pelletier. 1979b. LH and testoster• Sanford, L. M., J. S. D. Winter, W. M. Palmer and B. E. one release in developing bulls following LH-RII Howland. 1974. The profile of LH and testoster• treatment: Effect of gonadectomy and chronic one secretion in the ram. Endocrinology 95:627. testosterone propionate pre-treatment. Acta lindo- Santen, R. J. 1975. Is aromatization of testosterone to crinol. 91:719. estradiol required for inhibition of luteinizing hor• Lincoln, G. A. 1976. Seasonal variation in the episodic mone secretion in men? J. Clin. Invest. 56:1555. secretion of luteinizing hormone and testosterone Santen, R. J. 1981. Independent control of luteinizing in the ram. J. Endocrinol. 69:213. hormone secretion by testosterone and estradiol in Lincoln, G. A. 1978. Hypothalamic control of the males. In: K. Fortherby and S. B. Pal (Eds.) Hor• testis in the ram. Int. J. Androl. 1:331. mones in Normal and Abnormal Human Tissues, Lincoln, G. A. and H. M. Fraser. 1 979. Blockage of p 459. Walter de Gruyter, New York. episodic secretion of luteinizing hormone in the Schams, D., S. Gombe, E. Schallenberger, V, Reinhard ram by the administration of antibodies to luteini• and R, Claus. 1978. Relationships between short- zing hormone releasing hormone. Biol. Reprod. term variations of LH, FSH, and testos• 21:1239. terone in peripheral plasma of prepubertal bulls. Lincoln, G. A., M. J. Peet and R. A. Cunningham. J. Reprod. Fertil. 54:145. 1977. Seasonal and circadian changes in the episo• Schanbacher, B. D. 1979a. Testosterone secretion in dic release of follicle-stimulating hormone, luteini• cryptorchid and intact bulls injected with gona- zing hormone and testosterone in rams exposed to dotropin-releasing hormone and luteinizing hor• artificial photoperiods. J. Endocrinol. 72:337. mone. Endocrinology 104:360. Lipsett, M. B. 1979. The role of testosterone and Schanbacher, B. D. 1979b. Relationship of in vitro other in regulation of LH. J. Steroid gonadotropin binding to bovine testes and the Biochcm. 11:659. onset of spermatogenesis. J. Anim, Sci. 48:591. MacLusky, N. 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