Chapter 4 Natural Synchronization Processes

Major endocrine systems for regulation of reproductive processes:

See Figure 4-1 for cows.
Types of glands:

Figure 4-1 Approximate location of the endocrine glands of the cow which secrete hormones that regulate reproduction.(Redrawn from Foley et al. 1972. Dairy Cattle: Principles. Practices, Rroblems, Profits. Lea and Febiger.) 

1) Endocrine glands:
Don't have ducts.
Secrete hormones internally into blood stream.

2) Exocrine glands:
Have ducts.
Secrete externally into ducts.
Definition of Hormones:
Chemical agents which are carried by the blood to cells within a target organ or other target cells where they regulate a specific physiological activity.

Definition of Receptor sites:

1) Recognition units in cells that have a high affinity for a particular hormone
2) Chemically: Protein
3) Hormone + receptor site¡æ initiates reactions within cell which bring about the specific physiological response within that bound hormone.
4) Location of receptor sites in a cell:
   Cytosol receptor: For steroid hormones Membrane receptor: For peptide or protein hormones
5) Concentration of receptor sites in a target organ:
   increase or decrease depending on the endocrine status of the animal.
   Chemical classes of reproductive hormones:

1) Peptide or protein hormones: See Table 4-1.
Soluble: in water
Denatured by strong acids, strong bases, heat¡æ physiologically inactive Systemical(i.v.i.m., s.c.) adminstration: effective
Oral administration: not effective

Figure 4-2 Metabolic pathway foe the synthesis of gonadal steroid hormones and the chemical structure of the three most important sex steroids.(Niswender et al. 1974. Reproduction in Farm Animals. (3rd ed.) ed. Hafez. Lea and Febiger.) 

2) Steroid hormones: See Figure 4-2
All steroid hormones: have cholesterol as a common precursor.
Soluble: in ether and other solvents used to extract lipids
Effectively absorbed through gastrointestinal tract
Less effective with oral administration than with systemic administration
Relative effectiveness of oral adminstration:
Natural estrogens: effective
Natural progestins or androgens: effective, but less
Synthetic progestins: effective
Functional classes of reproductive hormones:
Primary hormones of reproduction: As in Table 4-2
* Abbreviations of hormones:
Peptide or Protein hormones: See Table 4-2
Estrone: E_1, Estradiol: E_2, Estriol: E₃
Progesterone: P_4, Testosterone: T
Secondary hormones of reproduction:
Thyroxine, Growth hormone, Insuline, etc

4-1 Primary reproductive hormones of pituitary gland

Pituitary(Hypophysis, Hypophyseal gland): in bony depression at base brain
embryologically and functionally two separate glands
Anterior pituitary(adenohypophysis)¡ç embryonic gut of mouth roof
GTH: FSH and LH in domestic animals
(LH=ICSH:Interstitial cell stimulating hormone in male)
prolactin(PRL): LTH(luteotropic hormone) in rodents
Posterior ptituitary(neurohypophysis)¡çembryonic brain, neuroendocrine gl.
Oxytocin
Hormone Action

FSH:

1)¡èfollicle growth
2)¡èestrogen production by granulosa cells in ovarian follicle
3)¡èinhibin secretion by granulosa cells with its production being enhanced by FSH and T

Inhibin:
¡éFSH secretion
In testes, and richer in folliclular fluid
4) In males: ¡èspermiogenesis
¢ÖSertoli cells:¡èinhibin and androgen binding porotein(ABP)
ABP = a carrier for T

LH:

1)¡èT from theca interna cells¡æ converted to estrogens by granulosa cells FSH¡è
2)¡èmaturation of oocytes and ovulation
3) luteotropic =¡èformation of CL(corpus luteum) & production of P₄
4) In males:¢ÖLeydig cells in interstitial tissue of testes¡æ¡èT and other androgens

PRL:

1) synergizes with LH: by ¡èLH receptor sites in CL in some species¡æ¡èP₄
2)¡èdevelopment of mammary gland and synthesis of milk
3) In males: synergizes with LH: by¡èLH receptor sites in Leydig cells¡æ¡èT

ACTH:

¡èrelease of glucocorticoids from adrenal cortex
Gluococorticoids: ¢Öparturition and synthesis of milk

In males:

FSH stimulates spermiogenesis in the testes with action on both spermatogonia and Sertoli cells.FSH stimulates the Sertoli cells to produce inhibin and androgen binding protein(ABP).Since inhibin has not been fully charaterized,it is frequently referred to as either testicular inhibin or ovatian inhibin,depending on its source.ABP is secreted into the lumen of the seminiferous tubles and serves as a carrier for testosterone.LH stumulates .Prolactin appears to synergize with LH by increasing hormone receptor sites LH in the testes.

Oxytocin,a peptide hormone released from posterior pituitary,stimulates the contraction of smooth muscle in the oviduct and uterus.Because of this activity,it has been postulated that oxytocin aids both sperm and ovum transport in the female tract and stimulates uterine contractions during paturition.Also,oxytocin stimilates the myoepithelial cells of the mammary gland,causing the ejection of milk.

4-2 Control of the pituitery Gland by the Hypothalamus

The hypothalamus is a neuroendocrine gland which forms along the floor and lateral wall of the third venticle of the brain.It is closely linked with the pituitary.The hypophyseal portal blood system connects the hypothalamus with anterior pituitary and is the route by which hormones of the hypothalamus reach the anterior pituitary.The hypothalamic hormones are released from terminals of axons(nerve fibers) into blood vessels which serve the anterior pituitary The area of the hypothalamus where this which recive releasing factors are median eminence and the ptituitary vessels which receive releasing factors the hypophyseal portal vessels.Also,a portion of the venous return from the nterior pituitary is by way of the hypothalamus.This permits a direct, short-loop feedback system whereby hormones of the anterior pituitary may help regulate release of hormones from the hypothalamus.The posterior pituitary is an extension of the hypothalamus.Axons from neurosecretory cells in the hypothalamus extends down into the posterior or pituitary(Figure 4-3).

Figure 4-3 Relationship between the hypothalamus and the pituitary gland 

Secretion of gonadotropic hormones from the anterior pituitary is controlled by a peptide-releasing hormone which is produced by neurosecretory cells in the hypothalamus. One peptide, gonadotropin releasing hormone(GnRH),has been isoalted and purified from pigs and sheep. GnRH causes the release of both FSH and LH. At one time, it was postulated that separate releasing agents (FSH-releasing hormone and LH-releasing hormone) regulated the release of FSH and LH from the anterior pituitary. While some physiological evidence for separate releasing hormones still exists, the preponderance of evidence supports a single releasing hormone for GSH and LH. In a clinical situation, GnRH can be used instead of LH for treatment of cystic ovaries in cows. There is evidence that both a prolactin releasing factor (PRF) and prolactin inhibiting factor (PIF) and prolactin inhibiting factor (PIF) control the release and retention of prolactin in the anterior pituitary. Corticotropin releasing hormone (CRH) stimulates the release of ACTH. A clearer picture of the functional nature of these releasing hormones should evolve in the near future. It is important that a link has been established between the central nervous system and function of the endocrine system.

Oxytocin, which is released from the posterior pituitary, is produced by the supraoptic and paraventricular unclei (neurosecretory cells) in the hypothalamus. After syntheses, oxytocin is transported by carrier proteins (neurophysins) as secretory droplets along nerve fibers extending into the posterior pituitary. Stimulation of sensory nerves in the teats or cervix will cause oxytocin to be released from nerve endings in the posterior pituitary.

4-3 Hormones of the Gonads

Major steroid hormones produced by the gonads are shown in Table 4-3.

4-3.1 Female

Two classes of hormones produced by the ovaries are estrogens and progestins. Chemically, estrogens and progestins are classifie as steroids and have cholesterol as a common precursor.

Estrogens, representing a group of steroids with similar physiological activity, are producedby specifid cells in the Graafian follicle. The thecal cells of the follicle are stimulated by LH to produce testosterone which diffuses across the basemint membrane, where it is converted to estorgens by granulosa cells under the influence of FSH. The estrogen of greatest importance, quantitatively and physiologically, is extradiol. Others of importance include estriol and estrone. The principal actions of estrogens are their influence on (1) the manifestation of mating behavior during estrus; (2) cyclic changesin the female tract; (3) duct development in the mammary gland; and (4) development of secondary sex characteristics in females. Estrogens have been called the "female sex hormone." Estrogens are luteolytic in cows and ewes but are luteotropic in sows.

Progestins are another group of hormones with similar physiological activity, the most impotrant being progesterone. They are produced by the granulosa cells in the corpus luteum under the influence of LH. Important functions are (1) inhibition of sexual behavior; (2) maintenance of pregnancy by inhibiting uterine contractions and promoting glandular developmint in the endometrium; and (3) promotion of alveolar developmint of the mammary gland. The symergistic actions of estrogesn and progestins are notable in preparing the uterus for pregnancy and the mammary gland for lactation.

Both estrogens and progestins help regulate the release of gonadotropins, acting through both the hypothalamus and anterior pituitary (Figure 4-4). High levels of either progestins or a combination of progestins and estrogens inhibit the release of GnRH, FSH, and LH from the anterior pituitary-a megative feedback control. Near the time of estrus, when progesterone levels are low, high estrogen concentrations action on the hypothalamus stimulate the release of GnRH, LH, FSH, and prolactin - a positive feedback control. The influence of the gonadotropins on estrogen and progestin release has been mentioned previously. Therefore, it can be seen that reciprocal action between the gonadotropins and the steroid hormones of the ovaries is necessary for maintenance of the hormone balance essential for normal reproduction.

Figure 4-4 Mechanism by which photoperiod regulates secretion of melatonin from the pineal gland. Nerve impulses resulting from phitic signals to the eye are transmitted from the retina along the retinohypothalamic tract to the suprachiasmatic nuclei and then to the superior cervical ganglia.

Inhibin, a protein hormone producd by granulosa cells in the voarian follicle, selectively suppresses release of FSH, but not LH, from the anterior pituitary. The action of inhibin may account for some of the reported differences in the release patterns of FSH an LH that appear inconsistent with a single gonadotropin releasing hormone.

Relaxin is a polypeptide hormone produced by the corpus luteum and placenta. Little is known about the mechanisms controlling its production,but higher concentrations are seen during pregnancy. It causes a relaxation of pelvic ligaments and softening of the connective tissue of the uterine muscles to allow the expansion necessary to accommodate the growing fetus. Synergizing with estrogen, it causes further expansion of the pelvis and softening of the connective tissue of the cervix to permit the fetus tobe expelled during parturition.

4-3.1a Follicular fluid

Follicular fluid(liquor folliculi) is the fluid that fills the antrum of a tertiary follicle bathing the granulosa cells. There is free exchange of fluids and many compounds btween blood and follicular fluid across the basemint membrane. However, large plasma proteins (>1,000,000 MW) do not cross the basement membrane and are not in follicular fluid. Follicular fluid is rich in steroid reproductive hormones including testosterone, estradiol, and progesterone. Concentrations of these steroids are much higher in follicular fluid than in blood. This is not surprising, since testosterone produced by theca cells is converted to estradiol in granulosa cells. As the follicle matures, the increasing number of granulosa cells is reflected by the decreased concentrtion of testosterone while estradiol concentration increases.

The pituitary hormones, FSH, LH, and prolactin,are found in follicular fluid. The lower concentrations of LH as compared to FSH may in part be due to binding of LH to theca cells outside the basement membrane, whereas granulosa cells have receptor sites for both FSH and LH. FSH is needed for the conversion of testosterone to estradiol by granulosa cells, whereas LH stimulates progesterone production by granulosa cells. Prolactin inhibits progesterone synthesis by granulosa cells (in vitro), and higher progesterone is seen in follicular fluid when prolactin is low. Prostaglandins are found in the follicular fluid of Graafian follicles as the time of ovulation approaches (Section 4-6)

Figure 4-5 Reationship between the hypothalamic releasing hormones, gonadotropins, and ovarian hormones in regrlating reproductive function

a. GnRH from thr hypothalamus stimulates the release of FSH and LH from the anterior potuitary.
b. FSH stimulates production of estradiol and inhibin by granulosa cells in the ovarian follicle.
c. Inhibin selecively inhibits release of FSH 
d. When progesterone is liw,high concentrations of estradiol stimulate a greater surge of GnRH, FSH, and LH, a positive feedback control.
e. LH stimulates production and release of progesterone by granulisa cells in the corpys luteum
f. High concentrations of progesterone ingibit the release of GnRH, FSH, and LH, a negative feedback control. 

A number of other peptide ovarian factors have been identified in follicular fluid in recent years. Of these, inhibin gas been characterized most completely and has been mentioned previously (Sections 4-1 and 4-3.1). It is a protein with various estimates on its molecular weight ranging from greater than 10,000 to greater than 70,000. Its production by granulosa cells is enhanced by both FSH and testosterone. Similarly, both FSH and testosterone have been reported to stimulate production of inhibin by Sertoli cells in the testes. Inhibin selectively inhibits production of FSH while not affecting LH in both females and males. Inhibin may serve to prevent overstimulation of the ovaries by FSH and may also be a factor in atresea (degeneration) of follicles that start development but do not ovulate during a given estrous cycle. Because its site of action is the anterior pituitary, a site away from the organ where it is produced, inhibin can be classified as a hormone.

GnRH or a simialr substance has been identified in follicular fluid. The concentrations in follicular fluid are thought to be too highfor it to be of hypothalamic origin,but cells in the ovary that secrete GnRH have not ben identified. GnRH will suppress production of estradiol and progesterone, thus interfering with ovulation and corpus luteum formation. The concentration of GnRH that originates from the hypothalamus is not high enough in peripheral blood to have these depressing effects on ovarian function.

Oocyte maturation inhibitor, a factor which prevents resumption of meiosis until a few hours before ovulation, may be produced by granulosa cells under the influence of FSH. A peptide with a molecular wight of less than 10,000, its activity declines shortly before ovulation, thereby permitting meiosis to resume. Other peptide factors with either stimulating or inhibiting effects on ovarian function are poorly characterized, but some will likely prove to be improtant to natural regulation of ovarian function. Factors that have been reported in research literature include luteinizing stimulator, luteinizing inhibitor, FSH receptor binding inhibitor, gonadostatin and gonadocrinin, the latter having actions similar to GnRH.

4-3.2 Male

Upon stimulation by LH, the Leydig cells of the testes produce androgens, which are a class of steroid hormones. The principal ndrogen in mature males is testosterone, which has been labeled the male sex hormone. Dihydrotestosterone is found in high enough concentration in peripheral tissue to be of tunctional importnce. Functions of testosterone include (1) development of secondary sex characteristics; (2) maintenance of the male duct system; (3) expression of male sexual behavior (libido); (4) function of the accessory glands; (5) function of the tunica dartos muscle in the scrotum; and (6) spermatocytogenesis. The role of testosterone in rgulating the release of hypothalamic and gonadotropic hormones is similar to that described for progesterone in the female (Figure 4-5). High concentrations of testosterone inhibit the release of GnRH, FSH, and LH,a negative feedback control. Conversely, when testosterone conecntrations are low, higher levels of GnRH, FSH, and LH are released. Thus, reciprocal action of testosterone with the hypothalamic and gonadotropic hormones is necessary for regulation of normal reproduction in the male. Inhibin anc androgen binding protein are produced by Sertoli cells under the influence of FSH. As in the female, inhibin selectively inhibits the release of FSH while not affecting the release of LH. Androgen binding protein binds testosterone, making it available for its functions in spermatozo production. Under the influence of FSH, Sertoli cells convert testosterone to estradiol, but a role for estradiol in regulation of reproduction in the male has not been clearly established.

Figure 4-6 Interrelationship of the hormones regulating reproduction in the male.

4-4 Primary Reproductive Hormones of the Adrenal Cortex

The adrenal cortex produces two classes of steroid hormones which have been associated with mineral metabolism (mineralocorticoid) and carbohydrate metabolism (glucocorticoids). Glucocorticoids, the principal one being cortisol, have been classified as anti-stress hormones, also. While progestins, estrogens, and androgens have been isolated from the adrenal cortex, they have not been seen in quantities high enough to affect the reproductive processes. Some think that they may be released at levels high enough to alter normal reproduction during periods of severe stress, but verification of this has been difficult.

A role for glucocortidoids in the initiation of parturition in sheep has been demonstrated. Furthermore, the glucocorticoids involved in this process ard of retal rather than maternal origin. This phenomenon has not been as clearly demonstrated in other classes of farm animals, but the evidence appears sufficiently strong to include glucocorticoids as a primary hormone of reproduction. In addtion, a role for glucocorticoids in milk synthesis has been advanced (Chapter 10).

4-5 Endocrine Runction of the Uterine/Placental Unit

The placenta does not fit the classical definition of an endocrine gland but does assume an endocrine function during pregnancy. Estrogens, progestins, and relaxin are produced by the placenta in certain species and supplement production of these hormones by the ovaries. In addition, placental hormone(s) with luteotropic and/or lactogenic activity have been identified in some species and may be present in athers. Human chorionic gonadotropin (HCG) has been sdolated from the urine of pregnant women. Its principal action is LH-like and is believed to help maintain the function of the corpus luteum during pregnancy. Pregnant mare serum gonadotropin (PMSG) is produced by endometrial cups which form when specialized cells in the chorion invade the endomitrium of the pregnant uterus of the mare. Principally, PMSG has FSH-like action but it has some LH-like activity, also. It has been isolated from the serum of mares during early pregnancy. A pregnancy has been postulated. Both HCG and PMSG are proteins. Placental lactogen has been isolated from a number of species including goats, sheep, and cows. It is a polypeptide and is extracted from the placenta of these species. Its properties are similar to both proalctin and growth hormone. Possible functions include development of the mammary gland for postpartum milk production, regulation of fetal growth through altered maternal or fetal metabolisn, and stimulation of progesterone synthesis by thd ovary or fetal metabolism, and stimulation of progesterone synthesis by the ovary or placenta. Higher concentrations are seen during late gestation than early gestation. Higher concentrations have also been reported for eows with high milk production than for low milk producers.

4-6 Reproductive Role of Prostaglandins

Prostaglandins are a group of biologically active lipids that have arachidonic acid, a 20-carbon, unsaturated fatty acid as their precursor. While prostaglandins have hormone-like actions, they do not fit the classic definition of a hormone. They are not produced by a specific gland or tissue. Rather, they are produced by cells throughout the body including cells in the uterus (female) and vesicular glands *male). In most cases they act locally at the site of their production, but in some cases their site of antion is in another tissue or organ. Prostaglandins are rapidly degraded in mammals with about 90% of their activity lost in one passage through the pulmonary circulation. Based on differences in chemical structure several parent prostaglandin compounds have been identified. Of these, prostaglandin E series (PGE) and prostaglandin F series (PGF) are of greatest viological interest. The two compounds most closely associated with reproduction are PGF₂¥á and PGE₂ (Figure 4-6)

Figure 4-7 Chemical structure of prostaglandin F2¥á(PGF2¥á)and prostaglandin E2(PGE2) 

PGF₂¥á is luteolytic (causes regression of the corpus luteum) and has a stimulating effect on smooth muscle. Because of these actions, natural functions in the control of the estrous cycoe, ovum transport, sperm transport, and parturition have been proposed. PGF₂¥á has been sued in clinical situations where regression of the corpus luteum or stimulation of smooth muscle is desired.

PGE₂ also appears to have an important role in reproduction. It is a smooth muscle stimulator, but its effect on the corpus luteum is opposite to that of PGF₂¥á. THe antiluteolytic action of PGE₂ may be a factor in the maintenance of early pregnancy by prevention PGF₂¥á induced luteolysis. Prostaglandins are found in the follicular fluid of Graafian follicles a few hours before ovulation and may be involved in the ovulation process. Inhibitors to prostaglandin synthesis have prevented ovulation in controlled experiments.

Little research has been reported on a orle for prostaglandins in the regulation of reproductive function in males. It has been demonstrated in bulls that injection of PGF₂¥á will cause a surge in LH and testosterone. However, an integrative role for prostaglandins in the natural regulation of reproductive function in males has not been determined.

4-7 The Pineal Gland

The pineal gland is located above the hypothalamus between the hemispheres of the brain. Its embryonic origin is the brain, but direct connection to the central nervous system is lost soon after birth with innervation there after coming from the sympathetic nerves. While the pineal gland of the amphibian has photoreceptors, they are not found in the pineal gland of mammals. However, the pineal gland of mammals is sensitive to environmental lighting and senses changes in photoperiod (day length). The eyes appear to be the sensor for the light stimulus with neural signals traveling by way of the optic nerve and other neural pathways to the pineal gland.

The pineal gland secretes melatonin, a derivative of the amino acid tryptophan. Melatonin has hormonal properties and will cause atrophy of the gonads along with cessation of reproductive function in male and female hamsters. Likewise, continuous darkness causes release of melatonin, atrophy of the gonads, and cessation of reproductive function. Darkness does not cause atrophy of the gonads if the pineal gland has been removed. Therefore, melatonin or some other factor from the pineal gland appears to be the means by which darkness depresses gonadal function. While darkness causes release of melatonin in sheep, antigonadal properties have not been demonstrated. However, interest remains high on a possible role of the pineal gland in regulation of seasonal breeding patterns in sheep, goats, and horses.

4-8 Regulation of Hormonal Receptor Sites

Hormone action is dependent on release of the hormone in question from its gland, transport to the target cells vea the circulatory system, and binding of the hormone to cellular receptor sites. After the hormone binds to the cellular receptor site, reactions are initiated within the cell to carry out the physiological response associated with the hormone.

The concentration of receptor sites for a specific hormone in a particular organ are dependent on the endocrine status of the animal. While research in thes area is relatively new, and limited mostly to laboratory anemals, some information is available on regulation of hormonal receptor sites. It provides a new basis for understanding how certain hormones synergize in regulating a physiological function. Patterns of regulation that can be seen are (1) hormones which regulate their own receptor sites; (2) synergism of two hormones to regulate the receptor sites of tons of the hormones; and (3) hormones which regulate receptors of other hormones. Up-regulation and down-regulation are terms that describe whether the number of receptors for a particular hormone are increased (induced) by the regulator or decreased by the regulator.

FSH up-regulates its own receptors in the ovarian follicle, but the up-regulation is speeded as estradiol concentrations increase. Also, FSH synergizes with estradiol to up-regulate follicular receptors for LH. Luteinizing hormone (LH) down-regulates its own receptors while at the same time inducing (up-regulating) receptors for prolactin. In the developing corpus luteum, prolactin increases receptors for LH and has been reported to prevent LH-induced loss of LH receptors. While this scheme of regulation was determined through reaearch with the rat ovary, many of these principles likely apply to other species. For example, LH will down-regulate its own receptors in the ovary of the ewe. While LH is the luteotropin in the ewe, some report that the luteotropic action cannot be maintained unless prolacin is present. By this, a role for prolactin in maintaining receptors for LH in the corpus luteum of the ewe can be suggested.

Figure 4-8 Intracellular mechanisms by which gonadotropins stimulate production of reproductive steroids. 

In the male, injection of FSH will decrease (down-regulate) the number of FSH receptors in the Sertoli cells of the testes. After a transient increase, LH receptors in Leydig cells decrease in response to administration of LH. While proalctin will maintain LH receptor concentration in Leydig cells, it is not clear whether this action occurs through prevention of LH-induced losses as has been reported in the female or by more direct up-regulation of LH receptors.

GnRH appears to regulate its own receptors in the anterior pituitary. Infusion of a high concentration of GnRH will down-regulate GnRH receptors, while low concentration infusion or intermittint doses will up-regulate GnRH receptors. The intermittent dose more closely parallels the physiological state, since intermittent surges of GnRH and LH occur in males and females. In the female these intermittent surges are more frequent near the time of estrus, thus making the anterior pituitary more sensitive to GnRH through an increased concentration of GnRH receptors. EStradiol enhances the effect of intermittent suges of GnRH on GnRH receptors, while progesterone of a combination of estradiol and progesterone inhibits this GnRH-induced response. Estrogen receptor concentrations in the anterior pituitary vary directly with the concentration of estrogens in the blood. Estrogen and progesterone receptors are found in the hypothalamus and anterior pituitary. Thes lends support to the hypothesis that these steroids exert feedback control on both the hypothalamus and the anterior tuitary.

In the uterus, estrogens up-regulate both estrogen and progesterone receptors. Increased binding of estradiol in the myometrium stimulates the appearance of more oxytocin receptors. Progesterone blocks synthesis of new estrogen receptors, resulting in a reduction in their concentration. Through this mechanism, progesterone down-regulates receptors for oxytocin. Thus, estrogens enhance the dffects of oxytocin on the myometrium while progesterone inhibits the oxytocic response.

4-9 Intracellular Mechanisms of Hormone Action

The mechanism by which gomadotropins stimualte a particular response from a cell involves a so-called "second messenger"system. The first messenger is the hormone. When the gonadotropic hormone binds to its membrane-bound receptor, it activates the membrane-bound enzyme, adenylate cyclase (Figure 4-7). The activated enzyme then stimulates the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) within the cytoplasm of the cell. Through a series of steps, cAMP (the second messenger) activates the enzymes needed to produce the steroik reproductive hormones. If LH binds to a membrane-bound receptor of a Leydig cell or a thecal cell, activation of the second messenger system will result in the production of testosterone. If LH binds to a membrand-bound receptor of a granulosa cell in the corpus luteum, progesterone will be produced. After stimulating the formation of cAMP within the cell, the fate of the hormone-receptor complex has not been determined. There is some evidence that it becomes internalized (taken into the cell) where it is degraded.

Figure 4-9 Intracellular mechanism by which steroid hormones have their action on target cells. 

The intracellular mechanism of action for steroid reproductive hormones (estradiol, progesterone, and testosterone) does not involve membrane receptors or a second messenger system. Rather, the steroid hormone passes through the cell membrane and binds to a protein receptor in the cytoplasm form the cytoplasm to the nucleus, where it initiates synthesis of specific messenger ribonucleic acid (mRNA) molecules from deox-yribonucleic acid (DNA) in chromosomes. This mRNA is then translocated to the cytoplasm, where synthesis of new protein occus. The newly synthesized protein is responsible for the biological activity of a steroid hormone on its target tissues.

4-10 Summary

Most of the hormonal regulation of the reproductive processes is contained in the hypothalamic-anterior pituitary-gonadal axis. Releasing hormones from the hypothalamus controls the function of the anterior pituitary. Gonadotropic hormones from the anterior pituitary control the function of the gonads, both in the production of gametes and hormones. In turn, through feedback mechanisms involving the hypothalamus, the steroid hormones and proteins of the gonads regulate the release of gonadotropins. These gonadal steroids also maintain optimum conditions for fertility through their effects on mating behavior and maintenance of the female and male duct systems. While other hormones have important regulatory functions in reproduction, their function is dependent on the reciprocal balance between the gonadotropic and steroid sex hormones. A greater appreciation for and understanding of the intricate balance needed for successful reproduction should evolve as the student progresses in his or her study of reproduction.